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miR-125a 通过抑制 GALNT14 的表达来调节卵巢癌细胞的增殖和侵袭。

MiR-125a regulates ovarian cancer proliferation and invasion by repressing GALNT14 expression.

机构信息

Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central south University, Changsha 410078, Hunan, PR China.

Cancer Research Institute, Central south University, Changsha 410078, Hunan, PR China.

出版信息

Biomed Pharmacother. 2016 May;80:381-387. doi: 10.1016/j.biopha.2015.12.027. Epub 2016 Apr 8.

Abstract

Increasing evidence has suggested that dysregulation of microRNAs (miRNAs) could contribute to tumor progression. The miR-125a was downregulated in several types of cancer, however, the molecular mechanism of miR-125a in the ovarian cancer remains unclear. The aim of the paper was to reveal the mechanism of miR-125a regulating cell proliferation and metastasis in ovarian cancer. In this study, western blotting, immunohistochemistry and serum-ELISA assay revealed that polypeptide N-acetylgalactosaminyl transferase 14 (GALNT14) expression was upregulated and correlated with the cancer stage in ovarian cancer. The expression levels of miR-125a were downregulated and negatively related to GALNT14 expression in clinical ovarian cancer tissues. Moreover, luciferase reporter assay identified polypeptide N-acetylgalactosaminyl transferase 14 (GALNT14) as a direct target of miR-125a, and overexpression of miR-125a markedly reduced the expression of GALNT14 in ovarian cancer. Functional characterization of miR-125a was accomplished by reconstitution of miR-125a and silencing GALNT14 expression in ovarian cancer cells to determine changes in proliferation and invasion. The MTT assay and transwell assay revealed that miR-125a transfectant significantly inhibits cell proliferation and invasion, by repressing GALNT14 expression. Furthermore, the gelatin zymography assay miR-125a mimics and GALNT14 siRNA suppressed the activity of MMP2 and MMP9. Taken together, our findings show that miR-125a functions as tumor suppressor in ovarian cancer by targeting GALNT14, and miR-125a may therefore serve as a biomarker for diagnosis and therapeutics in ovarian cancer.

摘要

越来越多的证据表明,miRNAs(microRNAs)的失调可能导致肿瘤的进展。miR-125a 在几种类型的癌症中下调,然而,miR-125a 在卵巢癌中的分子机制尚不清楚。本文的目的是揭示 miR-125a 调节卵巢癌细胞增殖和转移的机制。在这项研究中,western blot、免疫组化和血清 ELISA 检测表明,多肽 N-乙酰半乳糖胺转移酶 14(GALNT14)的表达上调,并与卵巢癌的癌症分期相关。miR-125a 的表达水平在临床卵巢癌组织中下调,并与 GALNT14 的表达呈负相关。此外,荧光素酶报告基因检测表明,多肽 N-乙酰半乳糖胺转移酶 14(GALNT14)是 miR-125a 的直接靶标,过表达 miR-125a 可显著降低卵巢癌细胞中 GALNT14 的表达。通过在卵巢癌细胞中重建 miR-125a 和沉默 GALNT14 表达来完成对 miR-125a 功能的表征,以确定增殖和侵袭的变化。MTT 检测和 Transwell 检测表明,miR-125a 转染体通过抑制 GALNT14 表达显著抑制细胞增殖和侵袭。此外,明胶酶谱分析 miR-125a 模拟物和 GALNT14 siRNA 抑制了 MMP2 和 MMP9 的活性。总之,我们的研究结果表明,miR-125a 通过靶向 GALNT14 发挥肿瘤抑制作用,在卵巢癌中,miR-125a 可能作为卵巢癌诊断和治疗的标志物。

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