Rs1347093 regulates microRNA-216/-217 expression and is associated with pancreatic cancer risk.

IF 2.8 2区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Pancreatology Pub Date : 2024-12-01 Epub Date: 2024-10-02 DOI:10.1016/j.pan.2024.10.004

Hsin-Hung Huang, Tzu-Yue Shiu, De-Chuan Chan, Chao-Feng Chang, Hsuan-Hwai Lin, Jung-Chun Lin, Peng-Jen Chen, Yu-Lueng Shih, Wei-Kuo Chang, Tsai-Yuan Hsieh

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引用次数: 0

Abstract

Background: Single nucleotide polymorphism (SNP) rs1347093 shows statistically significant association with lung cancer risk, but there is no further rs1347093 expression quantitative trait loci (eQTL) effect information. SNP rs1347093 is located in microRNA-216/-217 (miR-216/-217) locus. In addition, miR-216/-217 have pancreas-enriched expressions. In this study, we examined a potential miR-216/-217 promoter region, and investigated the effect of rs1347093-A allele on the miR-216/-217 promoter activity.

Methods: Bioinformatics analysis, quantitative real-time PCR, luciferase reporter assay, Western blotting, and cell counting kit-8 (CCK-8) assay were performed.

Results: The miR-216/-217 expressions are down-regulated in pancreatic cancer. In pancreatic cancer patients carrying the rs1347093-A allele, miR-216/-217 expressions were more largely suppressed. We identified a potential promoter region in miR-216/-217 locus and further showed that rs1347093-A allele resulted in significantly reduced promoter activity in pancreatic cancer cells, which could be mediated by MEF2C activities. In terms of mechanism in the pathogenesis of pancreatic cancer, miR-216b-5p expression was down-regulated, thereby preventing it from interacting with beclin-1 mRNA while promoting the survival of pancreatic cancer cells.

Conclusions: This study may reveal the biological relevance underlying rs1347093-A allele with an increase in pancreatic cancer risk. SNP rs1347093 could be meaningful as a novel biomarker for pancreatic cancer risk.

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Rs1347093 可调控 microRNA-216/-217 的表达，并与胰腺癌风险有关。

背景：单核苷酸多态性（SNP）rs1347093与肺癌风险有显著的统计学关联，但没有进一步的rs1347093表达量性状位点（eQTL）效应信息。SNP rs1347093位于microRNA-216/-217（miR-216/-217）位点。此外，miR-216/-217 在胰腺中有丰富的表达。本研究考察了潜在的miR-216/-217启动子区域，并研究了rs1347093-A等位基因对miR-216/-217启动子活性的影响：方法：进行生物信息学分析、定量实时 PCR、荧光素酶报告分析、Western 印迹和细胞计数试剂盒-8（CCK-8）检测：结果：miR-216/-217 在胰腺癌中表达下调。在携带 rs1347093-A 等位基因的胰腺癌患者中，miR-216/-217 的表达在很大程度上受到抑制。我们确定了 miR-216/-217 位点的潜在启动子区域，并进一步发现 rs1347093-A 等位基因会导致胰腺癌细胞启动子活性显著降低，而这可能是由 MEF2C 活性介导的。从胰腺癌的发病机制来看，miR-216b-5p的表达被下调，从而阻止了它与beclin-1 mRNA的相互作用，同时促进了胰腺癌细胞的生存：本研究可能揭示了rs1347093-A等位基因增加胰腺癌风险的生物学相关性。SNP rs1347093可作为胰腺癌风险的新型生物标记物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pancreatology 医学-胃肠肝病学

CiteScore

7.20

自引率

5.60%

发文量

194

审稿时长

44 days

期刊介绍： Pancreatology is the official journal of the International Association of Pancreatology (IAP), the European Pancreatic Club (EPC) and several national societies and study groups around the world. Dedicated to the understanding and treatment of exocrine as well as endocrine pancreatic disease, this multidisciplinary periodical publishes original basic, translational and clinical pancreatic research from a range of fields including gastroenterology, oncology, surgery, pharmacology, cellular and molecular biology as well as endocrinology, immunology and epidemiology. Readers can expect to gain new insights into pancreatic physiology and into the pathogenesis, diagnosis, therapeutic approaches and prognosis of pancreatic diseases. The journal features original articles, case reports, consensus guidelines and topical, cutting edge reviews, thus representing a source of valuable, novel information for clinical and basic researchers alike.