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Colorectal cancer (CRC) is an aggressive tumor, whose development is considered to be modulated by certain long non­coding RNAs (lncRNAs). Therefore, the aim of the present study was to investigate the regulatory mechanism of lncRNA NONHSAG028908.3 on CRC. Data from The Cancer Genome Atlas (TCGA) database revealed that NONHSAG028908.3 was increased in CRC tissues compared with normal tissues (P<0.001). The results of reverse transcription­quantitative PCR indicated that NONHSAG028908.3 was upregulated in four types of CRC cells compared with that in NCM460, a normal colorectal cell line. MTT, BrdU, and flow cytometric assays were applied to evaluate CRC cell growth. The migratory and invasive abilities of CRC cells were detected using wound healing and Transwell assays. Silencing of NONHSAG028908.3 inhibited proliferation, migration, and invasion of CRC cells. A dual­luciferase reporter assay demonstrated that NONHSAG028908.3 served as a sponge to combine with microRNA (miR)­34a­5p. MiR­34a­5p suppressed the aggressiveness of CRC cells. The effects induced by NONHSAG028908.3 knockdown were partly reversed by inhibition of miR­34a­5p. Furthermore, miR­34a­5p, a target of NONHSAG028908.3, modulated aldolase, fructose­bisphosphate A (ALDOA) expression in a negative feedback manner. Suppression of NONHSAG028908.3 notably decreased ALDOA expression, which was rescued via silencing of miR­34a­5p. Moreover, suppression of ALDOA revealed the inhibitory action on CRC cell growth and migration. In summary, the data of the present study indicate that NONHSAG028908.3 may positively regulate ALDOA via sponging miR­34a­5p, thereby promoting malignant activities in CRC.

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BACKGROUND: Long non-coding RNAs (lncRNAs) are essential indicators for hepatocellular carcinoma. LncRNAs can exert the same functions as their antisense mRNAs. ILF3 is an oncogene in hepatocellular carcinoma. ILF3 divergent transcript (ILF3-AS1) is the antisense RNA of ILF3, and has been reported as an oncogene in various cancers. AIMS: To explore the role of lncRNA ILF3-AS1 in malignant phenotypes of hepatocellular carcinoma cells. METHODS AND RESULTS: RT-qPCR analysis revealed that ILF3-AS1 was significantly upregulated in hepatocellular carcinoma cells. The hepatocellular carcinoma cell viability was suppressed by silenced ILF3-AS1. Transwell and wound healing assays showed that ILF3-AS1 downregulation inhibited cell invasion and migration. The levels of proteins associated with epithelial-mesenchymal transition (EMT) process and the Notch pathway were detected by western blot analysis. Luciferase reporter, RNA pull down and RIP assays were used to investigate the relationship between ILF3-AS1 and downstream target genes. ILF3-AS1 competed with meis homeobox 2 (MEIS2) for miR-628-5p in hepatocellular carcinoma cells. ILF3-AS1 elevated the levels of key proteins on the Notch pathway. Rescue assays demonstrated that MEIS2 reversed the antitumor effects of silenced ILF3-AS1 on hepatocellular carcinoma. In vivo assays demonstrated that ILF3-AS1 silencing inhibited the hepatocellular carcinoma tumor growth. CONCLUSIONS: ILF3-AS1 promoted hepatocellular carcinoma progression via the Notch pathway and miR-628-5p/MEIS2 axis.

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BACKGROUND: Surgical resection is considered the standard treatment option for long-term survival in colorectal cancer liver metastasis (CRLM) patients, but only a small number of patients are suitable for resection following diagnosis. Radiofrequency ablation (RFA) is an accepted alternative therapy for CRLM patients who are not suitable for resection. However, the relatively high rate of local tumor progression (LTP) is an obstacle to the more widespread use of RFA. AIM: To determine the oncological outcomes and predictors of RFA in CRLM patients. METHODS: A retrospective analyze was performed on the clinical data of 85 consecutive CRLM patients with a combined total of 138 liver metastases, who had received percutaneous RFA treatment at our institution from January 2013 to December 2018. Contrast-enhanced computed tomography was performed the first month after RFA to assess the technique effectiveness of the RFA and to serve as a baseline for subsequent evaluations. The Kaplan-Meier method was used to calculate overall survival (OS) and LTP-free survival (LTPFS). The log-rank test and Cox regression model were used for univariate and multivariate analyses to determine the predictors of the oncological outcomes. RESULTS: There were no RFA procedure-related deaths, and the technique effectiveness of the treatment was 89.1% (123/138). The median follow-up time was 30 mo. The LTP rate was 32.6% (45/138), and the median OS was 36 mo. The 1-, 3-, and 5-year OS rates were 90.6%, 45.6%, and 22.9%, respectively. Univariate analysis revealed that tumor size and ablative margin were the factors influencing LTPFS, while extrahepatic disease (EHD), tumor number, and tumor size were the factors influencing OS. Multivariate analysis showed that tumor size larger than 3 cm and ablative margin of 5 mm or smaller were the independent predictors of shorter LTPFS, while tumor number greater than 1, size larger than 3 cm, and presence of EHD were the independent predictors of shorter OS. CONCLUSION: RFA is a safe and effective treatment method for CRLM. Tumor size and ablative margin are the important factors affecting LTPFS. Tumor number, tumor size, and EHD are also critical factors for OS.

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Breast cancer (BC) is the most commonly diagnosed malignant cancer in women. BC is the main cause of cancer­related death in women and seriously threatens the life and health of women worldwide. MicroRNAs (miRNAs/miRs) have been reported to regulate the development and progression of different types of cancer. However, the regulatory functions of miR­188­5p in BC have not been thoroughly demonstrated. In this present research, we identified that miR­188­5p was downregulated in BC tissues and several BC cell lines. Downregulation of miR­188­5p was significantly associated with advanced TNM stage. Moreover, we identified that miR­188­5p mimics significantly inhibited proliferation using CCK­8 assay, colony formation and xenograft animal model, suppressed invasion and migration detected by Transwell invasion assay, and increased the cellular apoptosis of BC cells as determined by cell apoptosis assay. Moreover miR­188­5p mimics also reduced the expression of NF­κB p65(Rel). To further investigate its regulatory mechanism, transcription factor zinc finger protein 91 (ZFP91) was predicted as the targeted protein of miR­188­5p by bioinformatic method. We confirmed their specific binding by dual luciferase (DLR) assay. We demonstrated that the overexpression of miR­188­5p significantly inhibited the expression of ZFP91 in BC cell lines and reduced the expression of NF­κB p65(Rel). An inverse correlation was found between the expression of miR­188­5p and ZFP91 in BC tissues. Importantly, we demonstrated that the restoration of ZFP91 was able to block the effect of miR­188­5p on the progression of MDA­MB­231 cells. Therefore, our study showed that miR­188­5p may be one of the important indicators and could inhibit the progression of human BC via targeting the ZFP91/NF­κB p65(Rel) signaling pathway, suggesting that miR­188­5p may be a promising future target for BC treatment.

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Vascular calcification (VC), which is associated with high cardiovascular morbidity and mortality in patients with chronic kidney disease, is promoted by the osteoblastic differentiation of vascular smooth muscle cells (VSMCs). The present study explored the functional roles and molecular mechanisms of the long noncoding RNA growth arrest-specific transcript 5 (GAS5) in VC. Our results indicated that GAS5 was clearly downregulated in calcified human aortic vascular smooth muscle cells (HASMCs). Functionally, we found that overexpression of GAS5 significantly attenuated the osteogenic differentiation and calcification of HASMCs induced by high levels of phosphorus. Moreover, miR-26-5p was identified to potentially bind to GAS5, and phosphatase and tensin homolog (PTEN) was determined to be a direct target of miR-26b-5p in HASMCs. Mechanistically, enforced expression of miR-26-5p significantly attenuated PTEN protein expression in HASMCs. Rescue experiments demonstrated that cotransfection of HASMCs with miR-26-5p mimics reduced the inhibition of Lv-GAS5 on osteogenic differentiation and calcification. As a result, GAS5 was confirmed to be an miR-26b-5p sponge and to thereby increase the expression of PTEN in HASMCs. In ex vivo models, GAS5 was significantly downregulated and its expression inversely related to the expression of miR-26b-5 and positively associated with the expression of PTEN in calcified aortic rings induced by high levels of phosphorus. Together, these results suggest that the GAS5/miR-26-5p/PTEN axis could serve as a potential therapeutic target for VC in patients with chronic kidney disease.

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BACKGROUND: Long non-coding RNAs (lncRNAs) play important roles in many diseases, including hepatocellular carcinoma (HCC). Autophagy is a metabolic pathway that facilitates cancer cell survival in response to stress. The relationship between autophagy and the lncRNA-activated by transforming growth factor beta (lncRNA-ATB) in HCC remains unknown. AIM: To explore the influence of lncRNA-ATB in regulating autophagy in HCC cells and the underlying mechanism. METHODS: In the present study, we evaluated lncRNA-ATB expression in tumor and adjacent non-tumor tissues from 72 HCC cases by real-time PCR. We evaluated the role of lncRNA-ATB in the proliferation and clonogenicity of HCC cells in vitro. The effect of lncRNA-ATB on autophagy was determined using a LC3-GFP reporter and transmission electron microscopy. Furthermore, the mechanism by which lncRNA-ATB regulates autophagy was explored by immunofluorescence staining, RNA immunoprecipitation (RIP), and Western blot. RESULTS: The expression of lncRNA-ATB was higher in HCC tissues than in normal liver tissues, and lncRNA-ATB expression was positively correlated with tumor size, TNM stage, and poorer survival of patients with HCC. Moreover, ectopic overexpression of lncRNA-ATB promoted cell proliferation and clonogenicnity of HCC cells in vitro. LncRNA-ATB promoted autophagy by activating Yes-associated protein (YAP). Moreover, lncRNA-ATB interacted with autophagy-related protein 5 (ATG5) mRNA and increased ATG5 expression. CONCLUSION: LncRNA-ATB regulates autophagy by activating YAP and increasing ATG5 expression. Our data demonstrate a novel function for lncRNA-ATB in autophagy and suggest that lncRNA-ATB plays an important role in HCC.

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AIM: Diabetes accelerates pro-atherogenic and pro-osteogenic phenotypes of vascular smooth muscle cells (VSMCs), an important process for vascular calcification. Reticulocalbin 2 (RCN2) is a candidate gene for atherosclerosis and involved in vascular remodeling in hypertension. However, the role of RCN2 in VSMCs calcification under diabetic conditions is unclear. MATERIALS AND METHODS: Expression of RCN2 and Runt-related transcription factor 2 (Runx2) in femoropopliteal arterial plaques was compared between type 2 diabetes mellitus (DM) and non-DM patients using immunohistochemical staining (IHCS). Human aortic VSMCs (HAVSMCs) were analyzed under RCN2 gene knockdown and overexpression conditions. Alizarin red staining and intracellular calcium deposition quantification were used to observe calcification induced in vitro under normal glucose or high glucose combined with ß-glycerol phosphoric acid conditions. The cells were investigated for gene modulation of osteogenic differentiation markers using Western blotting. KEY FINDINGS: The expression of RCN2 and Runx2 in femoropopliteal artery plaques was significantly higher in DM than in non-DM patients. In addition, a significant positive correlation was observed between RCN2 and Runx2 levels. RCN2 was highly expressed when HAVSMCs were treated with high glucose and the expression levels correlated with the calcification characteristics. RCN2 upregulated osteogenic transformation markers Runx2 and Osterix in HAVSMCs and downregulated contractile phenotype markers α-SMA and SM22α. SIGNIFICANCE: The results from this study indicate RCN2 is a major factor in mediating the calcification process of HAVSMCs in diabetic conditions. Thus, RCN2 may serve as a future therapeutic target for vascular calcification in diabetes.

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