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Both the soybean variety and processing method affect the end soybean product's characteristics. This study's objective was to characterize the effects of four extraction methods (variations of soaking and grinding) combined with cooking on the content and composition of phenolic substances and the antioxidant and anti-DU145 prostate cancer cell proliferation properties of soymilks prepared from a yellow soybean of the ProSoy variety, which is a high-protein variety. The results showed that the soymilk processing yield was the greatest using method 4, although method 2 gave the highest solid and protein yields by about 14 and 12%, respectively. Method 4, a two-step grinding method, also gave increased yields (8 and 7% for solids and proteins, respectively), and in all but one instance produced higher total phenolic content (TPC), total flavonoid content (TFC), condensed tannin content (CTC), and total isoflavone content values in both raw and cooked soymilks as compared to method 1. Cooking the soymilks reduced 14-17% of their total phenolic substances. Cooking reduced the anti-cancer capacity of the phenolic extracts from the soymilk prepared using method 4 by increasing the IC50 value from about 4.9 mg/mL to 6.8 mg/mL. The increases in phenolic compounds and antioxidants produced in the Prosoy soymilks using methods 2 and 4, with simultaneous increases in product and solid yields, are of significant benefit to the soymilk industry and consumer health.

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This study aims to elucidate the mechanisms by which the effective components of Scleromitrion diffusum (Willd.) (SDW) treat lung cancer, using network pharmacology, in vitro cell experiments, and molecular docking methods. Network pharmacology techniques were employed to construct a network of SDW components, lung cancer targets, and signaling pathways. A proteinprotein interaction (P P I) network was built for target genes, identifying core gene targets. Signaling pathway and biological process analyses were conducted. MT T assays measured cell viability, and Western blot analysis assessed the impact of core protein targets and key pathway proteins on the stemness of three lung cancer cell lines. Molecular docking was performed to link SDW components with core proteins and key pathway targets related to lung cancer. SDW was found to target 88 genes and 5 active components (2-methoxy-3-methyl-9-10-anthraquinone, stigmasterol, beta-sitosterol, quercetin, and poriferasterol) relevant to lung cancer treatment. The P I3K/Akt and MEK/ERK pathways were identified as major signaling pathways. Extracts from SDW roots significantly inhibited the proliferation of three lung cancer cell lines (A549, HCC827, and NCIH-1395), primarily via P I3K/Akt and MEK/ERK pathways, significantly reducing the expression of p-Akt and p-Erk1/2 and slightly inhibiting caspase-9, p-P I3K, and EGFR expression. Molecular docking confirmed the strong binding activities of SDW components with lung cancer-related core proteins and key pathway targets. SDW may regulate apoptosis and proliferation in lung cancer treatment through P I3K-Akt and MAP K/ERK signaling pathways. The combination of network pharmacology, molecular docking, and experimental validation provides valuable insights into the molecular mechanisms of SDW in lung cancer therapy.

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BACKGROUND/AIM: A role for cold-shock domain (CSD) proteins in abnormal cell proliferation has been suggested in the literature. The aim of this study was to investigate the effect of hepatocyte growth factor (HGF)-induced up-regulation of CSD protein A (CSDA) expression on vascular endothelial growth factor (VEGF) expression and its role in gastric cancer cell invasion and proliferation. MATERIALS AND METHODS: We assessed effects on two gastric cancer cell lines using reverse transcription-polymerase chain reaction, western blotting, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, and CSDA knockdown with short hairpin RNA. RESULTS: Hepatocyte growth factor (HGF) elevates CSDA levels in gastric cancer cell lines. To elucidate the mechanism by which HGF prompts CSDA expression and its impact on vascular endothelial growth factor (VEGF), we applied the Mitogen Activated Protein Kinase (MAPK) inhibitor PD098059 and conducted analyses using western blot. Following the administration of PD098059, a reduction in the protein levels of HGF-stimulated VEGF was observed. Additionally, silencing of CSDA resulted in diminished levels of both VEGF and phosphorylated extracellular signal-regulated kinase (ERK). The suppression of CSDA also led to reduced HGF-induced cell proliferation and diminished invasive capabilities in vitro. Furthermore, our research pinpointed a potential activator protein-1 (AP-1) binding site within the VEGF promoter zone, validating its activity via chromatin immunoprecipitation assays. Electrophoretic mobility shift assays further disclosed that HGF-induced CSDA augmentation correlates with an increase in AP-1 binding to VEGF. CONCLUSION: CSDA is crucial for the proliferation of gastric cancer cells, and the inhibition of this protein could impede the advancement of gastric cancer.

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Breast cancer (BC) is among the top three most prevalent cancers across the world, especially in women, and its pathogenesis is still unknown. Fatty acid ß-oxidation is highly associated with breast cancer. Serpin family E member 1 (SERPINE1)-induced down-regulation of fatty acid ß-oxidation can facilitate BC cell proliferation, invasion, and metastasis. In this paper, the difference of miR-30d-5p expressions in both cancerous tissues and para-carcinoma tissues was first detected. Next, the expressions of SERPINE1, long-chain acyl-CoA dehydrogenase (LCAD) and medium-chain acyl-CoA dehydrogenase (MCAD) in the aforementioned tissues were analyzed. Finally, miR-30d-5p mimics were supplemented to breast cancer cells to observe the miR-30d-5p effect upon breast cancer cells. Via immunofluorescence assay and Western blotting, it was found that cancerous tissues had lower expressions of miR-30d-5p, MCAD and LCAD and a higher expression of SERPINE1 than para-carcinoma tissues. The miR-30d-5p mimic group had a decreased SERPINE1 expression and increased MCAD and LCAD expressions compared with the NC group, thus inhibiting BC cell proliferation, invasion, and metastasis. To sum up, miR-30d-5p blocks the cell proliferation, invasion and metastasis by targeting SERPINE1 and promoting fatty acid ß-oxidation. Preclinical studies are further required to establish a fatty acid ß-oxidation-targeting therapy for breast cancer.

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Silent mating type information regulation 2 homolog 1 (SIRT1) is a class III histone deacetylase (HDAC) that is NAD + dependent and essential for metabolism, senescence, and cell survival. SIRT1 is overexpressed in several cancers, including breast cancer. SIRT1 is a well-known target gene of the estrogen receptor alpha (ER alpha) and is closely related to ER alpha deacetylation. Transcription factor Estrogen-related receptors (ERRs) share sequence homology with ERs in the DNA-binding domain, therefore, the possibility of sharing target genes between them is high. Our current research aims to gain insight into the function of ERRß in regulating the activity of SIRT1 during the progression of breast cancer. ER-positive (ER + ve) breast cancer cells and tissues had considerably enhanced SIRT1 expression. Six potential ERRE sites were identified by analysis of the 5' upstream region of SIRT1, and both in vitro and in vivo experiments supported their presence. We found SIRT1 to be up-regulated in ERRß overexpressed ER + ve breast cancer cells. Furthermore, our findings suggested that ectopic production of ERR and PCAF would increase SIRT1 activity. Our findings also indicated that ectopic production of ERRß and PCAF increased SIRT1 activity. With sufficient evidence demonstrating the substantial involvement of SIRT1 in cell proliferation, migration, and colony formation capability, we were also able to illustrate the tumorigenic role of SIRT1. Overall, our findings highlight SIRT1's tumorigenic influence on breast cancer and suggest that SIRT1 inhibitors might serve as potential therapeutic drugs for the treatment of breast cancer.

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Various cells in our body regularly divide to replace old cells and dead cells. For a living cell to be growing, cell division and differentiation is highly essential. Cancer is characterised by uncontrollable cell division and invasion of other tissues due to dysregulation in the cell cycle. An accumulation of genetic changes or mutations develops through different physical (UV and other radiations), chemical (chewing and smoking of tobacco, chemical pollutants/mutagens), biological (viruses) and hereditary factors that can lead to cancer. Now, cancer is considered as a major death-causing factor worldwide. Due to advancements in technology, treatment like chemotherapy, radiation therapy, bone marrow transplant, immunotherapy, hormone therapy and many more in the rows. Although, it also has some side effects like fatigue, hair fall, anaemia, nausea and vomiting, constipation. Modern improved drug therapies come with severe side effects. There is need for safer, more effective, low-cost treatment with lesser side-effects. Biologically active natural products derived from plants are the emerging strategy to deal with cancer proliferation. Moreover, they possess anti-carcinogenic, anti-proliferative and anti-mutagenic properties with reduced side effects. They also detoxify and remove reactive substances formed by carcinogenic agents. In this article, we discuss different plant-based products and their mechanism of action against cancer.

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INTRODUCTION: Numerous genetic and biological processes have been linked to the function of microRNAs (miRNAs), which regulate gene expression by targeting messenger RNA (mRNA). It is commonly acknowledged that miRNAs play a role in the development of disease and the embryology of mammals. METHOD: To further understand its function in the oncogenic process, the expression of the miRNA profile in cancer has been investigated. Despite being referred to as a noteworthy miRNA in cancer, it is unknown whether hsa-miR-1225-5p plays a part in the in vitro progression of the luminal A and luminal B subtypes of breast cancer. We proposed that a synthetic hsa-miR-1225-5p molecule be expressed in breast cancer cell lines and its activity be evaluated with the aim of studying its function in the development of luminal breast cancer. In terms of the typical cancer progression stages, such as proliferation, survival, migration, and invasion, we investigated the role of hsa-miR-1225-5p in luminal A and B breast cancer cell lines. RESULTS: Additionally, using bioinformatics databases, we thoroughly explored the target score-based prediction of miRNA-mRNA interaction. Our study showed that the expression of miR-1225-5p significantly inhibited the in vitro growth of luminal A and B breast cancer cell lines. CONCLUSION: The results were supported by a bioinformatic analysis and a detailed gene network that boosts the activation of signaling pathways required for cancer progression.

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The cytokine tumor necrosis factor (TNF) plays a crucial role in the proliferation and metastasis of colorectal cancer (CRC) cells, but the underlying mechanisms remain poorly understood. Here, we report that chondroitin polymerizing factor 2 (CHPF2) promotes CRC cell proliferation and metastasis mediated by TNF, independently of its enzymatic activity. CHPF2 is highly expressed in CRC, and its elevated expression is associated with poor prognosis of CRC patients. Mechanistically, upon TNF stimulation, CHPF2 is phosphorylated at the T588 residue by MEK, enabling CHPF2 to interact with both TAK1 and IKKα. This interaction enhances the binding of TAK1 and IKKα, leading to increased phosphorylation of the IKK complex and activation of NF-κB signaling. As a result, the expression of early growth factors (EGR1) is upregulated to promote CRC cell proliferation and metastasis. In contrast, introduction of a phospho-deficient T588A mutation in CHPF2 weakened the interaction between CHPF2 and TAK1, thus impairing NF-κB signaling. CHPF2 T588A mutation reduced the ability of CHPF2 to promote the proliferation and metastasis of CRC in vitro and in vivo. Furthermore, the NF-κB RELA subunit promotes CHPF2 expression, further amplifying TNF-induced NF-κB signaling activation. These findings identify a moonlighting function of CHPF2 in promoting tumor cell proliferation and metastasis and provide insights into the mechanism by which CHPF2 amplifies TNF-mediated NF-κB signaling activation. Our study provides a molecular basic for the development of therapeutic strategies for CRC treatment.

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N6-methyladenosine (m6A) and N7-methylguanosine (m7G) modification of RNA represent two major intracellular post-transcriptional regulation modes of gene expression. However, the crosstalk of these two epigenetic modifications in tumorigenesis remain poorly understood. Here, we show that m6A methyltransferase METTL3-mediated METTL1 promotes cell proliferation of head and neck squamous cell carcinoma (HNSC) through m7G modification of the cell-cycle regulator CDK4. By mining the database GEPIA, METTL1 was shown to be up-regulated in a broad spectrum of human cancers and correlated with patient clinical outcomes, particularly in HNSC. Mechanistically, METTL3 methylates METTL1 mRNA and mediates its elevation in HNSC via m6A. Functionally, over-expression of METTL1 enhances HNSC cell growth and facilitates cell-cycle progress, while METTL1 knockdown represses these biological behaviors. Moreover, METTL1 physically binds to CDK4 transcript and regulates its m7G modification level to stabilize CDK4. Importantly, the inhibitory effects of METTL1 knockdown on the proliferation of HNSC, esophageal cancer (ESCA), stomach adenocarcinoma (STAD), and colon adenocarcinoma (COAD) were significantly mitigated by over-expression of CDK4. Taken together, this study expands the understanding of epigenetic mechanisms involved in tumorigenesis and identifies the METTL1/CDK4 axis as a potential therapeutic target for digestive system tumors.

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Glioblastomas (GBs) are one of the most aggressive and invasive intracranial cancers. Recently, it has been postulated that, among other factors, the hedgehog (HH) pathway may be a key factor in this phenomenon. Moreover, it has been reported that small-size silver nanoparticles (AgNPs) are characterized by a high cytotoxic effect towards GBs. However, their effect on the sonic hedgehog (SHH) pathway has never been demonstrated in any cancer cells. Therefore, the aim of the present study was to evaluate the impact of the anti-proliferative properties of 5-nm AgNPs on the SHH pathway in the GB cell line (U-87MG) in vitro. The results showed a time- and dose-dependent decrease in the metabolic activity in the U-87MG cells treated with AgNPs, with IC50 reaching 30.41 and 21.16 µg/mL after 24 h and 48 h, respectively, followed by an increase in the intracellular reactive oxygen species (ROS) level. The co-treatment of the cells with AgNPs and Robotnikinin (SHH inhibitor) abolished and/or strengthened the effect of AgNPs, especially on the SHH mRNA levels and on the PCNA, PTCH1, Gli1, and SUFU protein levels. Interestingly, no changes in the level of ERK1/2, Akt, and SRC kinase protein expression were detected, suggesting a direct impact of AgNPs and/or ROS on the inhibition of the canonical SHH pathway. However, more studies are needed due to the increase in the mTOR protein expression after the treatment of the cells with AgNPs, as in the Robotnikinin treatment. In conclusion, small-size AgNPs are able to inhibit the proliferation of GB cells in vitro by suppressing the canonical SHH pathway.

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Cancer is responsible for more than 10 million deaths every year. Metastasis and drug resistance lead to a poor survival rate and are a major therapeutic challenge. Substantial evidence demonstrates that an increasing number of long non-coding RNAs are dysregulated in cancer, including the long intergenic non-coding RNA, regulator of reprogramming (linc-ROR), which mostly exerts its role as an onco-lncRNA acting as a competing endogenous RNA that sequesters micro RNAs. Although the properties of linc-ROR in relation to some cancers have been reviewed in the past, active research appends evidence constantly to a better comprehension of the role of linc-ROR in different stages of cancer. Moreover, the molecular details and some recent papers have been omitted or partially reported, thus the importance of this review aimed to contribute to the up-to-date understanding of linc-ROR and its implication in cancer tumorigenesis, progression, metastasis, and chemoresistance. As the involvement of linc-ROR in cancer is elucidated, an improvement in diagnostic and prognostic tools could promote and advance in targeted and specific therapies in precision oncology.

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Breast cancer is the globally most common malignant tumor and the biggest threat to women. Even though the diagnosis and treatment of breast cancer are progressing continually, a large number of breast cancer patients eventually develop a metastatic tumor, especially triple-negative breast cancer (TNBC). Recently, metal ion homeostasis and ion signaling pathway have become important targets for cancer therapy. In this study, We analyzed the effects and mechanisms of isopimaric acid (IPA), an ion channel regulator, on the proliferation and metastasis of breast cancer cells (4 T1, MDA-MB-231and MCF-7) by cell functional assay, flow cytometry, western blot, proteomics and other techniques in vitro and in vivo. Results found that IPA significantly inhibited the proliferation and metastasis of breast cancer cells (especially 4 T1). Further studies on the anti-tumor mechanism of IPA suggested that IPA might affect EMT and Wnt signaling pathways by targeting mitochondria oxidative phosphorylation and Ca2+ signaling pathways, and then inducing breast cancer cell cycle arrest and apoptosis. Our research reveals the therapeutic value of IPA in breast cancer and provides a theoretical basis for the new treatment of breast cancer.

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Anthracyclines such as doxorubicin (Dox) are widely used to treat a variety of adult and childhood cancers, however, a major limitation to many of these compounds is their propensity for inducing heart failure. A naturally occurring polyphenolic compound such as Ellagic acid (EA) has been shown by our laboratory to mitigate the cardiotoxic effects of Dox, however, the effects of EA on cancer cell viability have not been established. In this study, we explored the effects of EA alone and in combination with Dox on cancer cell viability and tumorigenesis. Herein, we show that EA induces cell cycle exit and reduces proliferation in colorectal cancer (HCT116) and breast adenocarcinoma cells (MCF7). We show that EA promotes cell cycle exit by a mechanism that inhibits mitochondrial dynamics protein Drp-1. EA treatment of HCT116 and MCF7 cells resulted in a hyperfused mitochondrial morphology that coincided with mitochondrial perturbations including loss of mitochondrial membrane potential, impaired respiratory capacity. Moreover, impaired mitochondrial function was accompanied by a reduction in cell cycle and proliferation markers, CDK1, Ki67, and Cyclin B. This resulted in a reduction in proliferation and widespread death of cancer cells. Furthermore, while Dox treatment alone promoted cell death in both HCT116 and MCF7 cancer cell lines, EA treatment lowered the effective dose of Dox to promote cell death. Hence, the findings of the present study reveal a previously unreported anti-tumor property of EA that impinges on mitochondrial dynamics protein, Drp-1 which is crucial for cell division and tumorigenesis. The ability of EA to lower the therapeutic threshold of Dox for inhibiting cancer cell growth may prove beneficial in reducing cardiotoxicity in cancer patients undergoing anthracycline therapy.

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Breast cancer (BC) is the second most common cause of brain metastasis onset in patients, with the cerebellum accounting for the 33% of cases. In the current study, using a 4T1 triple-negative mouse BC model, we revealed that an orally administered medicinal mushrooms (MM) blend, rich in ß-glucans, played a direct and specific anti-cancer action on cerebellar metastases, also bettering locomotor performances. The neuroprotective effect of the MM blend plays through (i) a direct and specific inhibition of cerebellar metastatization pattern typical of TNBC (with an induced reduction of about 50% of metastases density) and (ii) the regulation of apoptosis and proliferation-related genes, as suggested by expression changes of specific molecular markers, i.e. PCNA, p53, Bcl2, BAX, CASP9, CASP3, Hsp70 and AIF. Therefore, inhibiting the metastatization process, triggering a significant apoptosis increase, and lessening cell proliferation, this MM supplement, employed as adjuvant treatment in association with conventional therapy, could represent a promising approach, in the field of Integrative Oncology, for patients' management in both prevention and treatment of brain metastases from BC.

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OBJECTIVE: To explore the relationship between CRYAB and the prognosis of prostate cancer (PCa) as well as the potential mechanism. METHODS: Bioinformatics analysis was performed using R software, including differential gene expression and clinical correlation analysis, receiver operating characteristic (ROC) curve and Kaplan-Meier (KM) curve generation. Gene expression was detected using RT-qPCR, and protein expression was validated using Western Blot. The proliferation, apoptosis, and metastatic ability of PCa cells were detected using CCK8, TUNEL, Transwell migration, and invasion assays. RESULTS: According to the TCGA and GEO databases, CRYAB mRNA expression was down-regulated in PCa tissue compared with normal tissue (P< 0.05), and CRYAB mRNA and protein were down-regulated in PCa cells compared with RWPE1 cells (P< 0.05). Cell function experiments showed that up-regulated CRYAB could inhibit the proliferation, invasion, and migration of prostate cancer cells, promote apoptosis (P< 0.05), and up-regulate CDH1 expression while down-regulating CDH2 expression in the CRYAB-upregulated cell line. In addition, CRYAB mRNA expression was correlated with Gleason score (P< 0.01). The area under the ROC curve was 0.914, the KM curve showed that CRYAB had prognostic value for progression-free survival (P = 0.008) and disease-specific survival (P = 0.032). CONCLUSION: CRYAB is down-regulated in PCa tissue and is associated with the anti- tumor function of PCa cells. It may affect the metastatic ability of prostate cancer cells by regulating epithelial-mesenchymal transition molecules. CRYAB mRNA has important diagnostic and prognostic value in PCa.

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BACKGROUND: Exosomes promote tumor growth and metastasis through intercellular communication, although the mechanism remains elusive. Carboxypeptidase E (CPE) supports the progression of different cancers, including hepatocellular carcinoma (HCC). Here, we investigated whether CPE is the bioactive cargo within exosomes, and whether it contributes to tumorigenesis, using HCC cell lines as a cancer model. METHODS: Exosomes were isolated from supernatant media of cancer cells, or human sera. mRNA and protein expression were analyzed using PCR and Western blot. Low-metastatic HCC97L cells were incubated with exosomes derived from high-metastatic HCC97H cells. In other experiments, HCC97H cells were incubated with CPE-shRNA-loaded exosomes. Cell proliferation and invasion were assessed using MTT, colony formation, and matrigel invasion assays. RESULTS: Exosomes released from cancer cells contain CPE mRNA and protein. CPE mRNA levels are enriched in exosomes secreted from high- versus low-metastastic cells, across various cancer types. In a pilot study, significantly higher CPE copy numbers were found in serum exosomes from cancer patients compared to healthy subjects. HCC97L cells, treated with exosomes derived from HCC97H cells, displayed enhanced proliferation and invasion; however, exosomes from HCC97H cells pre-treated with CPE-shRNA failed to promote proliferation. When HEK293T exosomes loaded with CPE-shRNA were incubated with HCC97H cells, the expression of CPE, Cyclin D1, a cell-cycle regulatory protein and c-myc, a proto-oncogene, were suppressed, resulting in the diminished proliferation of HCC97H cells. CONCLUSIONS: We identified CPE as an exosomal bioactive molecule driving the growth and invasion of low-metastatic HCC cells. CPE-shRNA loaded exosomes can inhibit malignant tumor cell proliferation via Cyclin D1 and c-MYC suppression. Thus, CPE is a key player in the exosome transmission of tumorigenesis, and the exosome-based delivery of CPE-shRNA offers a potential treatment for tumor progression. Notably, measuring CPE transcript levels in serum exosomes from cancer patients could have potential liquid biopsy applications.

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Recent studies have demonstrated that lncRNAs play an important role in cancers, particularly osteosarcoma. ZFAS1 is a newly identified and characterized lncRNA linked to a variety of cancers. The role of ZFAS1 in osteosarcoma is mainly unknown. This study discovered that ZFAS1 was upregulated in osteosarcoma patient tissues, which correlates with elevated SRSF3 protein levels. Higher levels of ZFAS1 or SRSF3 were linked to a poor prognosis of osteosarcoma. ZFAS1 knockdown decreased SRSF3 protein levels but had a negligible effect on SRSF3 mRNA expression. Further research indicated that ZFAS1 could bind to the SRSF3 protein directly and prevent degrading. Functional studies revealed that ZFAS1 knockdown inhibited osteosarcoma cell proliferation as measured by the CCK-8 assay, colony formation assay, and Ki-67 immunofluorescence staining. Furthermore, ZFAS1 knockdown reduced the expression of PCNA, CDK1, CDK4, and CDK6, increasing p53 and p16. IT has also been observed that ZFAS1 knockdown inhibited osteosarcoma cell migration and invasion as measured by the wound healing assay and the trans-well assay with or without Matrigel.Furthermore, exogenous SRSF3 expression in ZFAS1-depleted osteosarcoma cells restored SRSF3 expression while simultaneously inhibiting cell proliferation and metastasis. Our findings show that ZFAS1 plays an essential role in osteosarcoma progression by stabilizing the SRSF3 protein. Our study provides novel insight into the role of ZFAS1 in osteosarcoma. ZFAS1 has the potential to be used as a prognostic biomarker as well as a therapeutic target in the treatment of osteosarcoma.

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BACKGROUND: Increased CCKBR expression density or frequency has been reported in many neoplasms. OBJECTIVE: We aimed to investigate whether CCKBR drives the growth of gastric cancer (GC) and its potential as a therapeutic target of immunotoxins. METHODS: A lentiviral interference system was used to generate CCKBR-knockdown gastric cancer cells. Cell Counting Kit-8 and clonogenic assays were used to evaluate cell proliferation. Woundhealing and cell invasion assays were performed to evaluate cell mobility. Cell cycle was analyzed by flow cytometry. Tumor growth in vivo was investigated using a heterologous tumor transplantation model in nude mice. In addition, we generated the immunotoxin FQ17P and evaluated the combining capacity and tumor cytotoxicity of FQ17P in vitro. RESULTS: Stable downregulation of CCKBR expression resulted in reduced proliferation, migration and invasion of BGC-823 and SGC-7901 cells. The impact of CCKBR on gastric cancer cells was further verified through CCKBR overexpression studies. Downregulation of CCKBR expression also inhibited the growth of gastric tumors in vivo. Furthermore, FQ17P killed CCKBR-overexpressing GC cells by specifically binding to CCKBR on the tumor cell surface. CONCLUSION: The CCKBR protein drives the growth, migration, and invasion of gastric cancer cells, and it might be a promising target for immunotoxin therapy based on its aberrant expression, functional binding interactions with gastrin, and subsequent internalization.

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Dysfunctional lipid metabolism is a known cause of cancer development and progression, yet little is known about the underlying molecular mechanisms that contribute to cancer progression. In this study, we demonstrate that fatty acid binding protein 5 (FABP5) is elevated in colon cancer tissue and this increased expression is linked to upregulation of the hypoxia-inducible factor-1 (HIF-1) signaling pathway. Under physiologically in vivo mimicked conditions via a polydimethylsiloxane (PDMS)-based three-dimensional (3D) culture chip, FABP5-knockdown colon cancer cells exhibited attenuated cell growth throughout the culture period. FABP5 was found to regulate HIF-1α protein levels and gene expression levels within the HIF-1α signaling pathway under hypoxic conditions. Our results provide evidence that supports the use of FABP5 as a prognostic factor in colon cancer. The FABP5/HIF-1α axis is a promising target for ameliorating fatty acid-triggered cancer progression.

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BACKGROUND: The incidence of lung cancer in Yunnan area ranks firstly in the world and underlying molecular mechanisms of lung cancer in Yunnan region are still unclear. We screened a novel potential oncogene CYP2S1 used mRNA microassay and bioinformation database. The function of CYP2S1 in lung cancer has not been reported. OBJECTIVE: To investigate the functions of CYP2S1 in lung cancer. METHODS: Immunohistochemistry and Real-time PCR were used to verify the expression of CYP2S1. Colony formation and Transwell assays were used to determine cell proliferation, invasion and migration. Xenograft assays were used to detected cell growth in vivo. RESULTS: CYP2S1 is significantly up-regulated in lung cancer tissues and cells. Knockdown CYP2S1 in lung cancer cells resulted in decrease cell proliferation, invasion and migration in vitro. Animal experiments showed downregulation of CYP2S1 inhibited lung cancer cell growth in vivo. GSEA analysis suggested that CYP2S1 played functions by regulating E2F targets and G2M checkpoint pathway which involved in cell cycle. Kaplan-Meier analysis indicated that patients with high CYP2S1 had markedly shorter event overall survival (OS) time. CONCLUSIONS: Our data demonstrate that CYP2S1 exerts tumor suppressor function in lung cancer. The high expression of CYP2S1 is an unfavorable prognostic marker for patient survival.

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