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首页> 外文期刊>Clinical and experimental pharmacology & physiology >Inhibition of micro RNA RNA ‐21‐3p suppresses proliferation as well as invasion and induces apoptosis by targeting RNA‐binding protein with multiple splicing through Smad4/extra cellular signal‐regulated protein kinase signalling pathway in human colorectal cancer HCT HCT 116 cells
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Inhibition of micro RNA RNA ‐21‐3p suppresses proliferation as well as invasion and induces apoptosis by targeting RNA‐binding protein with multiple splicing through Smad4/extra cellular signal‐regulated protein kinase signalling pathway in human colorectal cancer HCT HCT 116 cells

机译:微RNA RNA -21-3P的抑制抑制增殖以及侵袭,并通过靶向RNA结合蛋白,通过SMAD4 /额外的细胞信号调节蛋白激酶信号传导途径靶向RNA结合蛋白,在人结肠癌HCT 116细胞中具有多重剪接

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摘要

Summary Micro RNA ‐21‐3p (miR‐21‐3p), the passenger strand of pre‐mir‐21, has been found to be high‐expressing in various cancers and to be associated with tumour malignancy, which is proposed as a novel focus in malignant tumours. Colorectal cancer ( CRC ), currently known as one of the most prevalent malignancy, is a leading cause of cancer death. This study aimed to investigate the key role of miR‐21‐3p in CRC by inhibiting its expression using transfection with miR‐21‐3p inhibitors into human CRC HCT 116 cells. Results showed that the expression of miR‐21‐3p was higher than other CRC cells used in the study including Lovo, HT 29, Colo320 and SW 480 cells, inhibition of which suppressed the proliferation and induced cell cycle arrest in HCT 116 cells. Besides, transfection with miR‐21‐3p inhibitors also attenuated cell migration and invasion, and induced apoptosis as well. Moreover, luciferase assay confirmed RBPMS as a direct target of miR‐21‐3p in HCT 116 cells. Further, miR‐21‐3p inhibitors increased the nuclear accumulation of Smad4 and reduced phosphorylation of ERK . Interestingly, we found that silence of RBPMS using RNA interference (si RNA ) not only elevated the cell viability but also increased the phosphorylation of ERK and reversed the nuclear accumulation of Smad4 induced by miR‐21‐3p inhibitors in HCT 116 cells. Data suggest that inhibition of miR‐21‐3p suppresses cell proliferation, invasion as well as migration and induces apoptosis by directly targeting RBPMS through Smad4/ ERK signalling pathway in HCT 116 cells. Our study demonstrates miR‐21‐3p as a potent target for suppressing tumour progression of CRC which may have implications in CRC therapy in the future.
机译:发明内容已发现乘客链的微RNA -21-3P(miR-21-3p),乘客链在各种癌症中具有高表达,并且与肿瘤恶性肿瘤相关,这是一个新颖的专注于恶性肿瘤。目前被称为最普遍的恶性肿瘤之一的结肠直肠癌(CRC)是癌症死亡的主要原因。本研究旨在通过用MiR-21-3P抑制剂转染在人CRC HCT 116细胞中来探讨CRC中miR-21-3P在CRC中的关键作用。结果表明,MiR-21-3P的表达高于研究中使用的其他CRC细胞,包括LOVO,HT 29,COLO320和SW 480细胞,其抑制在HCT116细胞中抑制了增殖和诱导细胞周期停滞。此外,用miR-21-3p抑制剂转染还减弱细胞迁移和侵袭,并诱导细胞凋亡。此外,荧光素酶测定法证实了RBPM作为HCT 116细胞中MiR-21-3P的直接靶标。此外,miR-21-3p抑制剂增加了Smad4的核积累,并降低了ERK的磷酸化。有趣的是,我们发现使用RNA干扰(Si RNA)的RBPMS沉默不仅升高了细胞活力,而且还增加了ERK的磷酸化并逆转了HCT 116细胞中MiR-21-3P抑制剂诱导的Smad4的核积累。数据表明,MiR-21-3P的抑制抑制细胞增殖,侵袭以及迁移,并通过在HCT 116细胞中直接靶向RBPM来诱导细胞凋亡。我们的研究表明miR-21-3p作为抑制CRC肿瘤进展的有效靶标,这可能对未来的CRC治疗有影响。

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