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长链非编码RNA MIR4435-2HG通过海绵吸附miR-128-3p调控ABHD17C促进胰腺癌进展。

Long non-coding RNA MIR4435-2HG promotes pancreatic cancer progression by regulating ABHD17C through sponging miR-128-3p.

作者信息

Chen Zhou, Du Yan, Shi Huaqing, Dong Shi, He Ru, Zhou Wence

机构信息

Department of General Surgery, The First School of Clinical Medicine, Lanzhou University, Lanzhou, China.

Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, China.

出版信息

Transl Cancer Res. 2024 Aug 31;13(8):4113-4130. doi: 10.21037/tcr-24-51. Epub 2024 Aug 23.

DOI:10.21037/tcr-24-51
PMID:39262472
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11385540/
Abstract

BACKGROUND

The recently identified carcinogenic long non-coding RNA (lncRNA) MIR4435-2HG has been validated to contribute to the initiation and progression of several malignancies. Nonetheless, its specific mechanistic function in pancreatic cancer (PC) is yet to be determined. This study aims to investigate the expression and functional role of MIR4435-2HG in PC and to elucidate its potential mechanism.

METHODS

This study employed The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx)-Pancreas datasets for the analysis of MIR4435-2HG expression in PC and normal pancreatic tissues and its relations with prognosis in PC. Moreover, quantitative real-time polymerase chain reaction (qRT-PCR) was employed for analyzing MIR4435-2HG, miR-128-3p, and ABHD17C expressions within cells and tissues. Cell proliferation and apoptosis were detected through Cell Counting Kit 8 (CCK-8) assay and flow cytometry while utilizing transwell and wound healing assays to assess cell migration and invasion. Predicting miR-128-3p binding sites with MIR4435-2HG or ABHD17C was conducted via the online tool starBase and validated through a dual-luciferase reporter (DLR), RNA pull-down and RNA binding protein immunoprecipitation (RIP) assays. Herein, we deployed Western blot to assess protein expression levels. The role of MIR4435-2HG was studied using tumor xenografts.

RESULTS

MIR4435-2HG overexpression exhibited a correlation with poor prognosis in PC. Knocking down MIR4435-2HG significantly hindered the proliferative, invading, and migrating PC cell abilities, accompanied by apoptosis induction, counteracted via a miR-128-3p inhibitor. Moreover, MIR4435-2HG could directly bind to miR-128-3p. Additionally, miR-128-3p directly targeted ABHD17C. Furthermore, as well as experiment results elucidated that knocking down MIR4435-2HG hindered PC progression by suppressing ABHD17C expression via miR-128-3p upregulation.

CONCLUSIONS

MIR4435-2HG can serve as a dependable target for PC diagnosis and treatment by modulating the miR-128-3p/ABHD17C axis to promote its progression.

摘要

背景

最近鉴定出的致癌长链非编码RNA（lncRNA）MIR4435-2HG已被证实与多种恶性肿瘤的发生和发展有关。然而，其在胰腺癌（PC）中的具体机制功能尚待确定。本研究旨在探讨MIR4435-2HG在PC中的表达及功能作用，并阐明其潜在机制。

方法

本研究使用癌症基因组图谱（TCGA）和基因型-组织表达（GTEx）-胰腺数据集分析PC和正常胰腺组织中MIR4435-2HG的表达及其与PC预后的关系。此外，采用定量实时聚合酶链反应（qRT-PCR）分析细胞和组织中MIR4435-2HG、miR-128-3p和ABHD17C的表达。通过细胞计数试剂盒8（CCK-8）检测和流式细胞术检测细胞增殖和凋亡，同时利用Transwell和伤口愈合试验评估细胞迁移和侵袭。通过在线工具starBase预测miR-128-3p与MIR4435-2HG或ABHD17C的结合位点，并通过双荧光素酶报告基因（DLR）、RNA下拉和RNA结合蛋白免疫沉淀（RIP）试验进行验证。在此，我们采用蛋白质印迹法评估蛋白质表达水平。利用肿瘤异种移植研究MIR4435-2HG的作用。

结果

MIR4435-2HG过表达与PC预后不良相关。敲低MIR4435-2HG显著阻碍PC细胞的增殖、侵袭和迁移能力，并诱导凋亡，miR-128-3p抑制剂可抵消这种作用。此外，MIR4435-2HG可直接与miR-128-3p结合。此外，miR-128-3p直接靶向ABHD17C。此外，实验结果表明，敲低MIR4435-2HG通过上调miR-128-3p抑制ABHD17C表达来阻碍PC进展。

结论

MIR4435-2HG可通过调节miR-128-3p/ABHD17C轴促进PC进展，作为PC诊断和治疗的可靠靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6618/11385540/57565469341e/tcr-13-08-4113-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6618/11385540/acc325b579d4/tcr-13-08-4113-f1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6618/11385540/57565469341e/tcr-13-08-4113-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6618/11385540/acc325b579d4/tcr-13-08-4113-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6618/11385540/b7e92e85b75e/tcr-13-08-4113-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6618/11385540/9bf758db83fc/tcr-13-08-4113-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6618/11385540/7e298058ee32/tcr-13-08-4113-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6618/11385540/6d0ebb5e735a/tcr-13-08-4113-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6618/11385540/606c703fac28/tcr-13-08-4113-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6618/11385540/57565469341e/tcr-13-08-4113-f7.jpg

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