shirin abdolvand
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Background
Cancer development is aided by the role of long noncoding RNAs (lncRNAs) that act as competing endogenous RNAs (ceRNAs) absorbing microRNAs (miRNAs). We aimed to discover a novel regulatory axis in colorectal cancer (CRC) and potential biomarkers based on miR‑616‑3p.
Materials and MethodsThe gene expression omnibus database was mined for differentially expressed lncRNAs (DELs) and mRNAs. LncRNAs and mRNAs were predicted using the RegRNA and TargetScan databases. A combination of the ciBioPortal and Ensemble databases was used to locate the mRNAs. Cytoscape 3.7.1‑built CeRNA networks. A quantitative real‑time polymerase chain reaction (qRT‑PCR) was utilized to confirm the expression levels of these RNA molecules. Statistical analyses were implemented by GraphPad Prism 9.
ResultsqRT‑PCR showed (Linc01282, lnc‑MYADM‑1:1, and Zinc Finger Protein 347 [ZNF347]) were overexpressed whereas, (salt‑inducible kinases 1 [SIK1], and miR‑616‑3p) were down regulated.
ConclusionThese results identify unique, unreported lncRNAs as CRC prognostic biomarkers, as well as prospective mRNAs as new treatment targets and predictive biomarkers for CRC. In addition, our study uncovered unexplored ceRNA networks that should be studied further in CRC.
Keywords: Colorectal cancer, linc01282, lnc‑MYADM‑1:1, microRNAs‑616‑3p, salt‑inducible kinases 1, ZNF347 -
Background
Long noncoding RNAs (lncRNAs) have been recognized as the main modulatory molecules in various cancers and perform as competing endogenous RNAs (ceRNAs). The nuclear hormone receptor superfamily of ligand?activated transcription factors (NR3C1) regulates numerous proliferative and metabolic processes such as tumorigenesis and metabolic diseases. Furthermore, X?linked inhibitor of apoptosis protein (XIAP) belongs to a family of the inhibitors of apoptosis proteins, is located downstream of the glucocorticoid receptor (GR or NR3C1) pathway, and cooperates with GR to suppress apoptosis. However, the underlying mechanisms of NR3C1 and XIAP in colorectal cancer (CRC) remain mainly unclear. This research aims to clarify the potential RNAbiomarkers and to construct a novel ceRNA network in CRC.
Materials and MethodsMultistep bioinformatics methods such as Lnc2cancer and miRDB databases were applied to identify candidate lncRNAs and miRNAs. The interaction energy between lncRNAs, NR3C1, and XIAP genes was analyzed by the LncRRIsearch database. Plus, microRNAs and lncRNA were evaluated via the Diana tools database to select microRNAs with the most binding scores. Quantitative reverse transcription– olymerase chain reaction (QRT?PCR) was applied to verify RNA molecules’ expression levels and their association with the clinicopathological factors in 30 CRC tissues compared to 30 adjacent tissues.
ResultsQRT?PCR showed upregulation of KCNQ1OT1, NR3C1, and XIAP and downregulation of miR?421. The ceRNA network was constructed with 17 lncRNAs, 2 mRNAs, and 42 miRNAs. Thus, we explained the potential interactions between KCNQ1OT1 and miR?421 with NR3C1 and XIAP genes.
ConclusionOur study represents potential prognostic biomarkers and a new ceRNA network for further study in CRC.
Keywords: Colorectal cancer, competing endogenous RNA, KCNQ1OT1, miR‑421, X‑linked inhibitor of apoptosis protein, NR3C1 -
زمینه و هدفشیوع سرطان معده در دو جنس متفاوت و به نسبت 2 به 1 در مردان شایع تر است. مهم ترین دلیل بیولوژیکی آن تفاوت هورمون های جنسی می باشد که می تواند منجر به تفاوت بیان ژن ها در دو جنس گردد و این به نوبه خود باعث تفاوت بروز بیماری ها در دو جنس می شود. اخیرا مطالعات نشان داده اند که miRNA ها در تفاوت بیان ژن ها نقش دارند. با توجه به وجود دو شکلی جنسیتی در بروز سرطان معده و عناصر پاسخ دهنده به هورمون های جنسی در ناحیه تنظیمی ژن های miR-146aو miR-148a ، در این مطالعه بیان این دو ژن در معده مردان و زنان سالم در گروه های سنی مختلف مقایسه شد.مواد و روش هابا استفاده از آندوسکوپی از ناحیه آنتروم معده 35 زن و 35 مرد سالم نمونه گیری شد. پس از استخراج RNA و سنتز cDNA (Complementary DNA)، بیان ژن های miR-146a و miR-148a در دو جنس با استفاده از تکنیک Real-time RT-PCR مقایسه شد و داده ها با آزمون های آماری تی مستقل و آنووا تجزیه و تحلیل گردید.یافته هابیان ژن های miR-146a و miR-148a در مردان و زنان تفاوت معنی داری را نشان نداد. بیان ژنmiR-146a در مردان زیر 45 سال به طور معنی داری بیش تر از مردان بالای 45 سال بود (p=0.017، 14 df= و t=1.47) و بیان ژن miR-148a در مردان بالای 45 سال به طور معنی داری بیش تر از مردان زیر 45 سال بود (p=0.001، df= 12 و t=1.28); در حالی که بیان هر دو ژن در زنان زیر 45 سال و زنان بالای 45 سال اختلافی را نشان نداد.نتیجه گیریبیان ژن miR-146a در معده ی مردان با افزایش سن کاهش می یابد، در حالی که بیان ژن miR-148a در معده ی مردان با افزایش سن افزایش می یابد.کلید واژگان: معده, ژن miR, 146a, ژن miR, 148a, تفاوت بیان ژن در دو جنس, هورمون های جنسیBackgroundThe incidence of gastric cancer is different in two sexes with ratio 2 to 1 that it is more common in men. The most important biologically reason is sexual hormones between two sexes that lead to sexual dimorphism and in turn can cause a sex bias in incidence of disease between two sexes. Recently, studies have shown that microRNA is involved in sexual dimorphism in gene expression. Given the sexual dimorphism in the incidence of gastric cancer and sex hormones response elements in the regulatory regions of miR-146a and miR-148a genes, in this study, the expression of these two genes in the stomach of healthy men and women at different age groups were compared.Materials And MethodsUsing endoscopy, gastric antrum tissues of 35 healthy women and 35 healthy men were collected. After RNA extraction and synthesis of cDNA, the expression of miR-146a and miR-148a genes were compared between sexes by Real time RT-PCR and data were analyzed using independent sample t and ANOVA tests.ResultsThere was no difference between men and women in genes expression of miR-146a and miR-148a. However, expression of miR-146a gene was significantly more in men under 45 years than men over 45 years (p= 0.017, df= 14, t= 1.47). Also, expression of miR-148a gene was significantly more in men over 45 years than men under 45 years (p=0.001, df= 12, t= 1.28). But the expression of both genes had no significant difference between women under 45 years and women over 45 years.ConclusionExpression of miR-146a and miR-148a genes in the stomach is increased and decreased with aging in men, respectively.Keywords: MiR-146a gene, MiR-148a gene, Sex hormones, Sexual dimorphism in gene expression, Stomach
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