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微小RNA-30d通过直接靶向GNA13基因,在结直肠癌的起始、进展和侵袭过程中发挥关键作用。

miRNA-30d serves a critical function in colorectal cancer initiation, progression and invasion via directly targeting the GNA13 gene.

作者信息

Muhammad Shan, Tang Qingchao, Wei Liu, Zhang Qian, Wang Guiyu, Muhammad Bilal Umar, Kaur Kavanjit, Kamchedalova Tatiana, Gang Zhao, Jiang Zheng, Liu Zheng, Wang Xishan

机构信息

Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.

Department of Pharmacology, Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.

出版信息

Exp Ther Med. 2019 Jan;17(1):260-272. doi: 10.3892/etm.2018.6902. Epub 2018 Oct 30.

Abstract

MicroRNAs (miRNAs or miRs) are reported to be dysregulated in the progression and invasion of various human cancer types, including colorectal cancer (CRC). They are also reported to be molecular biomarkers and therapeutic targets in CRC. miRNAs serve functions in a plethora of biological processes, including proliferation, migration, invasion and apoptosis, and several miRNAs have been demonstrated to be involved in CRC carcinogenesis, invasion and metastasis. Aberrant miR-30d expression and its effects have been reported in certain cancer types. However, the function and underlying mechanism of miR-30d in the progression of CRC remains largely unknown. In the current study, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to quantify miR-30d expression in CRC tissues. and functional assays indicated that miR-30d inhibits CRC cell proliferation. Target prediction online software packages, miRBase, TargetScan and miRANDA, and luciferase reporter assays were used to confirm the target gene GNA13. Specimens from 45 patients with CRC were analyzed for correlation between the expression of miR-30d and the expression of target gene GNA13, evaluated by RT-qPCR. miR-30d was downregulated in CRC tissues and cell lines. Ectopic expression of miR-30d inhibited cell proliferation and invasion and tumor growth ability. By contrast, inhibition of endogenous miR-30d promoted cell proliferation and tumor growth ability of CRC cells. It was indicated that miR-30d directly targets the 3'-untranslated region of the GNA13 gene. Downregulation of miR-30d led to the activation of cell proliferation in CRC. In addition, miR-30d expression was negatively correlated with the expression of GNA13 in CRC tissues. In conclusion, miR-30d inhibits cancer initiation, proliferation and invasion in colorectal cancer via targeting GNA13.

摘要

据报道,微小RNA(miRNA或miR)在包括结直肠癌(CRC)在内的多种人类癌症类型的进展和侵袭过程中表达失调。它们还被报道为CRC的分子生物标志物和治疗靶点。miRNA在众多生物学过程中发挥作用,包括增殖、迁移、侵袭和凋亡,并且已证实几种miRNA参与CRC的致癌作用、侵袭和转移。在某些癌症类型中已报道了miR - 30d的异常表达及其作用。然而,miR - 30d在CRC进展中的功能和潜在机制仍 largely unknown。在本研究中,进行了逆转录定量聚合酶链反应(RT - qPCR)以量化CRC组织中miR - 30d的表达。功能测定表明miR - 30d抑制CRC细胞增殖。使用在线靶标预测软件包miRBase、TargetScan和miRANDA以及荧光素酶报告基因测定来确认靶基因GNA13。通过RT - qPCR分析了45例CRC患者的标本中miR - 30d表达与靶基因GNA13表达之间的相关性。miR - 30d在CRC组织和细胞系中表达下调。miR - 30d的异位表达抑制细胞增殖、侵袭和肿瘤生长能力。相比之下,抑制内源性miR - 30d可促进CRC细胞的增殖和肿瘤生长能力。结果表明miR - 30d直接靶向GNA13基因的3'非翻译区。miR - 30d的下调导致CRC中细胞增殖的激活。此外,miR - 30d表达与CRC组织中GNA13的表达呈负相关。总之,miR - 30d通过靶向GNA13抑制结直肠癌的癌症起始、增殖和侵袭。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55bc/6307398/0a287e83f152/etm-17-01-0260-g00.jpg

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