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miR-26a-5p 通过抑制宫颈癌细胞中的羟甾类脱氢酶 2 来调节增殖、凋亡、迁移和侵袭。

MiR-26a-5p regulates proliferation, apoptosis, migration and invasion via inhibiting hydroxysteroid dehydrogenase like-2 in cervical cancer cell.

机构信息

Hunan Province Key Laboratory for Antibody-Based Drug and Intelligent Delivery System, Hunan University of Medicine, Huaihua, 418000, Hunan, China.

Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair, Guilin Medical University, Guilin, 541001, Guangxi, China.

出版信息

BMC Cancer. 2022 Aug 10;22(1):876. doi: 10.1186/s12885-022-09970-x.

Abstract

BACKGROUND

Evidences have indicated that miR-26a-5p regulates the malignant properties of various tumor cells. However, the influences of miR-26a-5p on proliferation, apoptosis and invasion are still vague in the cervical cancer (CC) cells.

METHODS

The miRNA microarray and real-time quantitative PCR (RT-qPCR) analysis were utilized to detect the expression of miR-26a-5p in the patients with CC. Kaplan-Meier plotter was performed to evaluate the overall survival (OS) of the patients with CC. The CCK-8, flow cytometry, transwell and wound healing analyses were respectively used to analyze proliferation, migration and invasion in the CC cells. RT-qPCR, western blot and IHC analysis were executed to measure the expression of hydroxysteroid dehydrogenase like-2 (HSDL2) in the patients with CC. Bioinformatics and luciferase reporter assay were carried out to verify the relationship of miR-26a-5p and HSDL2.

RESULTS

The expression of miR-26a-5p was downregulated and low expression of miR-26a-5p indicated a poor OS in patients with CC. Overexpression of miR-26a-5p significantly inhibited proliferation, migration and invasion, accelerated apoptosis in the Hela and C33A cells. The expression of HSDL2 was upregulated, and negatively correlated with miR-26a-5p in the patients with CC. HSDL2 was directly targeted by miR-26a-5p and rescue experiments displayed that HSDL2 partially abolished proliferation, apoptosis, migration, and invasion induced by miR-26a-5p in CC cells.

CONCLUSIONS

MiR-26a-5p alleviated progression of CC by suppressing proliferation, migration and invasion, promoting apoptosis through downregulating HSDL2.

摘要

背景

有证据表明,miR-26a-5p 调节各种肿瘤细胞的恶性特性。然而,miR-26a-5p 对宫颈癌(CC)细胞增殖、凋亡和侵袭的影响仍不清楚。

方法

利用 miRNA 微阵列和实时定量 PCR(RT-qPCR)分析检测 CC 患者 miR-26a-5p 的表达。Kaplan-Meier 绘图器评估 CC 患者的总生存期(OS)。CCK-8、流式细胞术、Transwell 和划痕愈合分析分别用于分析 CC 细胞的增殖、迁移和侵袭。RT-qPCR、western blot 和 IHC 分析用于测量 CC 患者 HSDL2 的表达。生物信息学和荧光素酶报告实验验证 miR-26a-5p 和 HSDL2 之间的关系。

结果

miR-26a-5p 的表达下调,miR-26a-5p 低表达表明 CC 患者 OS 不良。miR-26a-5p 的过表达显著抑制 Hela 和 C33A 细胞的增殖、迁移和侵袭,加速凋亡。CC 患者 HSDL2 的表达上调,与 miR-26a-5p 呈负相关。HSDL2 是 miR-26a-5p 的直接靶点,挽救实验显示 HSDL2 部分消除了 miR-26a-5p 在 CC 细胞中诱导的增殖、凋亡、迁移和侵袭。

结论

miR-26a-5p 通过下调 HSDL2 抑制增殖、迁移和侵袭,促进凋亡,从而减轻 CC 的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af78/9367141/ab1ad6593eb1/12885_2022_9970_Fig1_HTML.jpg

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