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微小RNA-665通过靶向SRCIN1促进卵巢癌细胞的增殖。

MicroRNA-665 promotes the proliferation of ovarian cancer cells by targeting SRCIN1.

作者信息

Zhou Ping, Xiong Tingchuan, Yao Lili, Yuan Jianlin

机构信息

Department of Gynecology and Obstetrics, Cancer Hospital Affiliated to Xinjiang Medical University, Ürümqi, Xinjiang 830011, P.R. China.

出版信息

Exp Ther Med. 2020 Feb;19(2):1112-1120. doi: 10.3892/etm.2019.8293. Epub 2019 Dec 5.

Abstract

Recent studies have discovered several microRNAs (miRNAs/miRs) as biomarkers for the prediction of ovarian cancer by detecting miRNA profiles in serum samples from healthy volunteers and patients with ovarian cancer. However, whether and how these miRNAs are involved in tumorigenesis is not known. In the present study, the expression of miR-665, a recently discovered biomarker for ovarian cancer, was upregulated in tumor tissues from patients with ovarian cancer compared with normal tissues. Inhibition of miR-665 inhibited cell proliferation ability and inactivated MAPK/ERK signaling of ovarian cancer cells. Using bioinformatics analysis, Src kinase signaling inhibitor 1 (SRCIN1) was predicted as a potential target gene of miR-665. Reverse transcription-quantitative PCR and western blotting showed that SRCIN1 expression was repressed by miR-665 in ovarian cancer cells. In addition, a dual luciferase activity assay showed that SRCIN1 was a target gene of miR-665. Silencing of SRCIN1 could reverse the cell growth arrest, which was induced by the miR-665 inhibitor. Moreover, miR-665 levels were negatively correlated with SRCIN1 mRNA levels in tumor tissues from patients with ovarian cancer. In conclusion, the present data suggested that miR-665 functioned as an oncogene in ovarian cancer by directly repressing the expression of SRCIN1.

摘要

最近的研究发现了几种微小RNA(miRNA/miR)作为预测卵巢癌的生物标志物,通过检测健康志愿者和卵巢癌患者血清样本中的miRNA谱来实现。然而,这些miRNA是否以及如何参与肿瘤发生尚不清楚。在本研究中,与正常组织相比,卵巢癌患者肿瘤组织中最近发现的卵巢癌生物标志物miR-665的表达上调。抑制miR-665可抑制卵巢癌细胞的增殖能力并使MAPK/ERK信号失活。通过生物信息学分析,预测Src激酶信号抑制剂1(SRCIN1)为miR-665的潜在靶基因。逆转录定量PCR和蛋白质印迹表明,miR-665在卵巢癌细胞中抑制SRCIN1的表达。此外,双荧光素酶活性测定表明SRCIN1是miR-665的靶基因。沉默SRCIN1可逆转由miR-665抑制剂诱导的细胞生长停滞。此外,在卵巢癌患者的肿瘤组织中,miR-665水平与SRCIN1 mRNA水平呈负相关。总之,目前的数据表明,miR-665通过直接抑制SRCIN1的表达在卵巢癌中发挥癌基因的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12fa/6966142/b6d7bb324242/etm-19-02-1112-g00.jpg

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