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Necroptosis can either be the cause of tumorigenesis or it can impede its process. Recently, it has been proved that long non-coding RNAs (lncRNAs) have different crucial roles at cellular level, especially on cell death. Regarding the important role of necroptosis and lncRNAs in the pathogenesis of different cancers, especially pituitary adenomas (PAs), we assessed expression levels of two necroptosis related genes, namely TRADD and BIRC2, in addition to three related lncRNAs, namely FLVCR1-DT, MAGI2-AS3, and NEAT1 in PAs compared with adjacent normal tissues (ANTs). TRADD had no significant difference between two groups; however, BIRC2, FLVCR1-DT, MAGI2-AS3, and NEAT1 were upregulated in PAs compared to ANTs (Expression ratios [95% CI] = 2.3 [1.47-3.6], 2.13 [1.02-4.44], 3.01 [1.76-5.16] and 2.47 [1.37-4.45], respectively). When taking into account different types of PAs, significant upregulation of BIRC2, MAGI2-AS3 and NEAT1 was recorded in non-functioning PAs compared with corresponding ANTs (Expression ratios [95% CI] =1.9 [1.04-3.43], 2.69 [1.26-5.72] and 2.22 [0.98-5.01], respectively). Additionally, higher levels of BIRC2 were associated with higher flow of CSF (P value=0.048). Moreover, higher Knosp classified tumors had lower levels of BIRC2 (P value=0.001). Finally, lower levels of MAGI2-AS3 were associated with larger tumor size (P value=0.006). NEAT1 expression was correlated with FLVCR1-DT and TRADD. TRADD expression was correlated with FLVCR1-DT. Additional correlation was observed between expression of BIRC2 and MAGI2-AS3. In sum, this study provides evidence that dysregulated levels of studied genes could contribute to the pathogenesis of pituitary tumors.

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Recent studies have revealed the impact of microRNAs (miRNAs) in the carcinogenic process. miR-424 is a miRNA whose role in this process is being to be identified. Experiments in the ovarian cancer, cervical cancer, hepatocellular carcinoma, neuroblastoma, breast cancer, osteosarcoma, intrahepatic cholangiocarcinoma, prostate cancer, endometrial cancer, non-small cell lung cancer, hemangioma and gastric cancer have reported down-regulation of miR-424. On the other hand, this miRNA has been found to be up-regulated in melanoma, laryngeal and esophageal squamous cell carcinomas, glioma, multiple myeloma and thyroid cancer. Expression of this miRNA is regulated by methylation status of its promoter. Besides, LINC00641, CCAT2, PVT1, LIN00657, LINC00511 and NNT-AS1 are among lncRNAs that act as molecular sponges for miR-424, thus regulating its expression. Moreover, several members of SNHG family of lncRNAs have been found to regulate expression of miR-424. This miRNA is also involved in the regulation of E2F transcription factors. The current review aims at summarization of the role of miR-424 in the process of cancer evolution and its impact on clinical outcome of patients in order to find appropriate markers for malignancies (AU)

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Non-functioning pituitary adenomas (NFPAs) are a group of pituitary neuroendocrine tumors that are associated with morbidity. The exact pathophysiological process leading to this pathology is not known. Nerve growth factor (NGF) is a neurotropic factor that might be involved in this process. We used bioinformatics tools to analyze expression of genes in NFPA samples. Our analyses led to identification of NGF-related genes, namely ARC, ID1, and SH3GL3 - as well as one long non-coding RNA (lncRNA) called myocardial infarction associated transcript (MIAT). Then, we assessed their expression in NFPAs and their adjacent non-cancerous samples. While expression levels of SH3GL3 and MIAT were different between NFPA samples and control samples, expressions of ARC and ID1 were not meaningfully different between these two groups of specimens. SH3GL3 was over-expressed in NFPA samples compared with control samples (expression ratio (95% CI)= 8.22 (1.51-44.6), P value= 0.03). Similarly, expression of MIAT was higher in NFPAs compared with controls (expression ratio (95% CI)= 7.7 (1.7-33.6), P value= 0.009). Taken together, we validated the bioinformatics results regarding the expression of SH3GL3 and MIAT. This study provides a deeper understanding of the involvement of these genes in the pituitary tumorigenesis.

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Fibrosis refers to excessive build-up of scar tissue and extracellular matrix components in different organs. In recent years, it has been revealed that different cytokines and chemokines, especially Transforming growth factor beta (TGF-ß) is involved in the pathogenesis of fibrosis. It has been shown that TGF-ß is upregulated in fibrotic tissues, and contributes to fibrosis by mediating pathways that are related to matrix preservation and fibroblasts differentiation. There is no doubt that antioxidants protect against different inflammatory conditions by reversing the effects of nitrogen, oxygen and sulfur-based reactive elements. Oxidative stress has a direct impact on chronic inflammation, and as results, prolonged inflammation ultimately results in fibrosis. Different types of antioxidants, in the forms of vitamins, natural compounds or synthetic ones, have been proven to be beneficial in the protection against fibrotic conditions both in vitro and in vivo. In this study, we reviewed the role of different compounds with antioxidant activity in induction or inhibition of TGF-ß/SMAD signalling pathway, with regard to different fibrotic conditions such as gastro-intestinal fibrosis, cardiac fibrosis, pulmonary fibrosis, skin fibrosis, renal fibrosis and also some rare cases of fibrosis, both in animal models and cell lines.

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Recent studies have revealed the impact of microRNAs (miRNAs) in the carcinogenic process. miR-424 is a miRNA whose role in this process is being to be identified. Experiments in the ovarian cancer, cervical cancer, hepatocellular carcinoma, neuroblastoma, breast cancer, osteosarcoma, intrahepatic cholangiocarcinoma, prostate cancer, endometrial cancer, non-small cell lung cancer, hemangioma and gastric cancer have reported down-regulation of miR-424. On the other hand, this miRNA has been found to be up-regulated in melanoma, laryngeal and esophageal squamous cell carcinomas, glioma, multiple myeloma and thyroid cancer. Expression of this miRNA is regulated by methylation status of its promoter. Besides, LINC00641, CCAT2, PVT1, LIN00657, LINC00511 and NNT-AS1 are among lncRNAs that act as molecular sponges for miR-424, thus regulating its expression. Moreover, several members of SNHG family of lncRNAs have been found to regulate expression of miR-424. This miRNA is also involved in the regulation of E2F transcription factors. The current review aims at summarization of the role of miR-424 in the process of cancer evolution and its impact on clinical outcome of patients in order to find appropriate markers for malignancies.

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Natural killer cells (NK cells) are a type of cytotoxic lymphocytes which are involved in innate immunity, alongside with assisting with adaptive immune response. Since they have cytotoxic effects, disruptions in their functionality and development leads to a variety of conditions, whether malignant or non-malignant. The profile and interaction of these non-coding RNAs and NK cells in different conditions is extensively studied, and it is now approved that if dysregulated, non-coding RNAs have detrimental effects on NK cell activity and can contribute to the pathogenesis of diverse disorders. In this review, we aim at a thorough inspection on the role of different non-coding RNAs on the activity and development of NK cells, in a broad spectrum of conditions, including blood-related disorders, viral infections, neurological diseases, gastrointestinal disorders, lung disorders, reproductive system conditions and other types of maladies, alongside with providing insight to the future non-coding RNA-NK cell studies.

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MINCR (MYC-Induced Long Non-Coding RNA) is classified as an lncRNA. It has a significant correlation with MYC gene. MINCR has important roles in the carcinogenesis. It has been approved that this lncRNA can act as molecular sponge for miR-28-5p, miR-708-5p, miR-876-5p and miR-146a-5p. Dysregulated levels of MINCR has been observed in different types of cancer, especially hepatocellular carcinoma. In addition to malignant conditions, schizophrenia and neurodegenerative diseases such as Alzheimer's disease and amyotrophic lateral sclerosis are associated with dysregulation of expression patterns of MINCR. This review outlines MINCR molecular mechanisms of action in different disorders.

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Sarcopenia is an elderly disease and is related to frailty and loss of muscle mass (atrophy) of older adults. The exact molecular mechanisms contributing to the pathogenesis of disease are yet to be discovered. In recent years, the role of noncoding RNAs in the pathogenesis of almost every kind of malignant and nonmalignant conditions is pinpointed. Regarding their regulatory function, there have been an increased number of studies on the role of noncoding RNAs in the progress of sarcopenia. In this manuscript, we review the role of microRNAs and long noncoding RNAs in development and progression of disease. We also discuss their potential as therapeutic targets in this condition.

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MAGI2 Antisense RNA 3 (MAGI2-AS3) is a long non-coding RNA (lncRNA) transcribed from a locus on 7q21.11. This lncRNA has been described to be abnormally expressed in a variety of malignancies in correlation with many clinical characteristics. Moreover, it might participate in the pathogenesis of congenital diaphragmatic hernia, Alzheimer's disease and intervertebral disc degeneration. Mechanistically, MAGI2-AS3 can serve as a molecular sponge for miR-142-3p, miR-424-5p, miR-15b, miR-233, miR-452-5p, miR-629-5p, miR-25, miR-155, miR-23a-3p, miR-519c-3p, miR-374b-5p, miR-374a, miR-31-5p, miR-3163, miR-525-5p, miR-15-5p, miR-374a-5p, miR-374b-5p, miR-218-5p, miR-141-3p and miR-200a-3p to regulate expression of their mRNA targets. The current review summarizes the role of MAGI2-AS3 in different disorders to highlight its importance in their pathophysiology.

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Long intergenic non-protein coding RNA 472 (LINC00472) has been shown to regulate diverse cellular functions and contribute to the etiology of human disorders. LINC00472 gene is located on 6q13 and has different alternatively spliced transcripts. Expression pattern and function of LINC00472 have been evaluated in different types of cancers and some other disorders, including atherosclerosis, sepsis-induced acute hepatic injury, atrial fibrillation, neuropathic pain, primary biliary cholangitis and sepsis-induced cardiac dysfunction. This lincRNA can serve as a sponge for miR-24-3p, miR-196b-5p, miR-23a-3p, miR-93-5p, miR-4311, miR-455-3p and a number of other miRNAs. LINC00472 is able to regulate several pathways, including MEK/ERK, NF-kB, PTEN/PI3K/AKT, and STAT3 signaling pathways. This raises some concerning aspects that need to be investigated further and clarified in relation to diseases. Increasing our understanding of LINC00472's crucial roles will open new doors for creating effective therapeutic approaches against cancer and related diseases. The current study aims at providing an overview of functions of LINC00472 in malignant and non-malignant disorders.

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ZEB1 Antisense RNA 1 (ZEB1-AS1) is a type of RNA characterized as long non-coding RNA (lncRNA). This lncRNA has important regulatory roles on its related gene, Zinc Finger E-Box Binding Homeobox 1 (ZEB1). In addition, role of ZEB1-AS1 has been approved in diverse malignancies such as colorectal cancer, breast cancer, glioma, hepatocellular carcinoma and gastric cancer. ZEB1-AS1 serves as a sponge for a number of microRNAs, namely miR-577, miR-335-5p, miR-101, miR-505-3p, miR-455-3p, miR-205, miR-23a, miR-365a-3p, miR-302b, miR-299-3p, miR-133a-3p, miR-200a, miR-200c, miR-342-3p, miR-214, miR-149-3p and miR-1224-5p. In addition to malignant conditions, ZEB1-AS1 has functional role in non-malignant conditions like diabetic nephropathy, diabetic lung, arthrosclerosis, Chlamydia trachomatis infection, pulmonary fibrosis and ischemic stroke. This review outlines different molecular mechanisms of ZEB1-AS1 in a variety of disorders and highlights its importance in their pathogenesis.

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NCK1 Antisense RNA 1 (NCK1-AS1), alternatively named as NCK1-DT, is a long non-coding RNA (lncRNA) with important roles in the carcinogenesis. Multiple studies verified its oncogenic role in different types of cancer, including gastric cancer, non-small cell lung cancer, glioma, prostate cancer and cervical cancer. NCK1-AS1 functions as a sponge for several microRNAs, including miR-137, miR-22-3p, miR-526b-5p, miR-512-5p, miR-138-2-3p and miR-6857. In this review we present an outline of NCK1-AS1 function in malignant conditions as well as atherosclerosis.

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Recent decade has seen a tremendous progress in identification of the role of different long non-coding RNAs (lncRNAs) in human pathologies. ADAMTS9-AS2 is an example of lncRNAs with different roles in human disorders. It is mostly acknowledged as a tumor suppressor lncRNA in different types of cancers. However, it has been reported to be up-regulated in tongue squamous cell carcinoma, salivary adenoid cystic carcinoma and glioblastoma. Moreover, ADAMTS9-AS2 is possibly involved in the pathoetiology of pulpitis, acute ischemic stroke, type 2 diabetes and its complications. This lncRNA sponges miR-196b-5p, miR-223-3p, miR-130a-5p, miR-600, miR-223-3p, miR-27a-3p, miR-32, miR-143-3p, miR-143-3p and miR-182-5p in order to regulate downstream mRNAs. This review aims at summarization of the role of ADAMTS9-AS2 in different disorders with a particular focus on its diagnostic and prognostic values.

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LINC00152 is an important lncRNA in human disorders. It is mainly regarded as a tumor-promoting lncRNA. Mechanistically, LINC00152 serves as a molecular sponge for miR-143a-3p, miR-125a-5p, miR-139, miR-215, miR-193a/b-3p, miR-16-5p, miR-206, miR-195, miR-138, miR-185-5p, miR-103, miR-612, miR-150, miR-107, miR-205-5p and miR-153-3p. In addition, it can regulate activity of mTOR, EGFR/PI3K/AKT, ERK/MAPK, Wnt/ß-Catenin, EGFR, NF-κB, HIF-1 and PTEN. In this review, we provide a concise but comprehensive explanation about the role of LINC00152 in tumor development and progression as well as its role in the pathology of non-malignant conditions with the aim of facilitating the clinical implementation of this lncRNA as a diagnostic or prognostic tumor marker and therapeutic target.

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Long non-coding RNAs are demonstrated to contribute to carcinogenesis. TMPO Antisense RNA 1 (TMPO-AS1) is an example of lncRNAs with crucial roles in this process. This lncRNA serves as a sponge for miR-320a, miR-383-5p, miR-329-3p, miR-126, miR-329, miR-199a-5p, miR-577, miR-4731-5p, miR-140-5p, miR-1179, miR-143-3p, miR-326, miR-383-5p, let-7c-5p, let-7g-5p, miR-199a-5p, miR-200c, miR-204-3p, miR-126-5p, miR-383-5p, miR-498, miR-143-3p, miR-98-5p, miR-140 and miR-143. It can also affect activity of PI3K/Akt/mTOR pathway. The current review summarizes the role of TMPO-AS1 in the carcinogenesis and assessment of its potential as a marker for certain types of cancers.

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miR-671 is encoded by a gene on 7q36.1 and contributes to the pathogenesis of a variety of disorders, including diverse types of cancers, atherosclerosis, ischemic stroke, liver fibrosis, osteoarthritis, Parkinson's disease, rheumatoid arthritis, acute myocardial infarction and Crohn's disease. In the context of cancer, different studies have revealed opposite roles for this miRNA. In brief, it has been shown to be down-regulated in pancreatic ductal carcinoma, ovarian cancer, gastric cancer, osteosarcoma, esophageal squamous cell carcinoma and myelodysplastic syndromes. Yet, miR-671 has been up-regulated in glioma, colorectal cancer, prostate cancer and hepatocellular carcinoma. Studies in breast, lung and renal cell carcinoma have reported inconsistent results. The current review aims at summarization of the role of miR-671 in these disorders focusing on its target mRNA in each context and dysregulated signaling pathways. We also provide a summary of the role of this miRNA as a prognostic factor in malignancies.