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

miRNA-30d 通过直接靶向 GNA13 基因在结直肠癌的发生、发展和侵袭中发挥关键作用

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

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. In vivo and in vitro 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.

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