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miRNA-15a-5p 靶向癌基因 YAP1 抑制宫颈癌细胞活力并诱导细胞凋亡。

MicroRNA‑15a‑5p‑targeting oncogene YAP1 inhibits cell viability and induces cell apoptosis in cervical cancer cells.

机构信息

Department of Obstetrics and Gynaecology, Huashan Hospital North, Fudan University, Shanghai 200040, P.R. China.

Department of Obstetrics and Gynaecology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China.

出版信息

Int J Mol Med. 2020 Oct;46(4):1301-1310. doi: 10.3892/ijmm.2020.4704. Epub 2020 Aug 12.

Abstract

MicroRNAs (miRNAs) have been reported to have important regulatory roles in the progression of several types of cancer, including cervical cancer (CC). However, the biological roles and regulatory mechanisms of miRNAs in CC remain to be fully elucidated. The aim of the present study was to examine the functions of miRNAs in CC and the possible mechanisms. Using a microarray, it was identified that miRNA‑15a‑5p (miR‑15a‑5p) was one of the most downregulated miRNAs in CC tissues compared with adjacent noncancerous tissues. The low expression of miR‑15a‑5p was observed in CC tumor tissues with distant metastasis and in CC cell lines. In addition, the effects of miR‑15a‑5p upregulation on cell viability, apoptosis, invasion and migration of CC cells were investigated using CCK‑8, flow cytometry, Transwell and wound healing assays, respectively. It was demonstrated that upregulation of miR‑15a‑5p significantly suppressed the viability, migration and invasion, and promoted the apoptosis of SiHa and C‑33A cells. Furthermore, yes‑associated protein 1 (YAP1), a well‑known oncogene, was confirmed to be directly targeted by miR‑15a‑5p and was found to be negatively regulated by miR‑15a‑5p. Further correlation analysis indicated that miR‑15a‑5p expression was negatively correlated with YAP1 expression in CC tissues. Notably, overexpression of YAP1 abrogated the tumor suppressive effects of miR‑15a‑5p in CC cells. Taken together, these present findings indicated that the miR‑15a‑5p/YAP1 axis may provide a novel strategy for the clinical treatment of CC.

摘要

微小 RNA(miRNA)已被报道在多种癌症的进展中具有重要的调节作用,包括宫颈癌(CC)。然而,miRNA 在 CC 中的生物学作用和调节机制仍有待充分阐明。本研究旨在研究 miRNA 在 CC 中的功能及其可能的机制。通过微阵列分析,发现 miRNA-15a-5p(miR-15a-5p)是与相邻非癌组织相比 CC 组织中下调最明显的 miRNA 之一。miR-15a-5p 在具有远处转移的 CC 肿瘤组织和 CC 细胞系中表达水平较低。此外,通过 CCK-8、流式细胞术、Transwell 和划痕愈合实验分别研究了 miR-15a-5p 上调对 CC 细胞活力、凋亡、侵袭和迁移的影响。结果表明,miR-15a-5p 的上调显著抑制了 SiHa 和 C-33A 细胞的活力、迁移和侵袭,并促进了其凋亡。此外,yes 相关蛋白 1(YAP1),一种众所周知的癌基因,被证实是 miR-15a-5p 的直接靶标,并且受到 miR-15a-5p 的负调控。进一步的相关性分析表明,miR-15a-5p 的表达与 CC 组织中 YAP1 的表达呈负相关。值得注意的是,YAP1 的过表达消除了 miR-15a-5p 在 CC 细胞中的肿瘤抑制作用。总之,这些研究结果表明,miR-15a-5p/YAP1 轴可能为 CC 的临床治疗提供新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5905/7447307/104a9a32f912/IJMM-46-04-1301-g00.jpg

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