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首页> 外文期刊>Cellular Physiology and Biochemistry >MicroRNA-21 (Mir-21) Promotes Cell Growth and Invasion by Repressing Tumor Suppressor PTEN in Colorectal Cancer
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MicroRNA-21 (Mir-21) Promotes Cell Growth and Invasion by Repressing Tumor Suppressor PTEN in Colorectal Cancer

机译：MicroRNA-21（Mir-21）通过抑制大肠癌中的肿瘤抑制因子PTEN促进细胞生长和侵袭

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>Background/Aims: MicroRNA-21 (miR-21) has been demonstrated to play an important role in carcinogenesis; however, its mechanism of action in colorectal cancer (CRC) has not been fully elucidated. The aim of the present study was to explore the oncogenic function of miR-21 and its molecular mechanism in CRC. Methods: A total of 105 paired tumor and tumor-adjacent normal tissue specimens from CRC patients and two CRC cell lines (HCT-116 and SW480) were studied. The protein and mRNA expression levels of PTEN and miR-21 were examined using western blot analysis and real-time reverse transcription-PCR (qRT-PCR). Furthermore, we transfected CRC cells with different combinations of ectopic-expression vector or shRNA expression vector of miR-21 and phosphatase and tensin homolog (PTEN) to modulate the expression levels of miR-21 and PTEN respectively, and then analyzed the phenotypic alterations of CRC cells. Tumorigenesis was also evaluated by xenografting HCT-116 cells into nude mice. Results: In this study, we showed that miR-21 expression was significantly up-regulated in CRC compared to that in normal tissues. Patients with advanced Tumor-Node-Metastasis (TNM) stage, lymph node metastasis, local invasion and higher serum carcinoembryonic antigen (CEA) levels displayed significantly high expression of miR-21. The PTEN protein level in CRC tissues and cells was inversely correlated with miR-21 expression. Furthermore, the transfection of CRC cells with pre-miR-21 could inhibit apoptosis and promote cellular proliferation, invasion, cell cycle progression and growth of xenografts in nude mice, whereas the transfection of miR-21-specific shRNA resulted in the opposite phenomena. In addition, silencing or elevating PTEN protein could partially reverse the effect of miR-21-specific shRNA or pre-miR-21 on apoptosis, cell cycle distribution, and invasion of CRC cells. Moreover, over-expression or knockdown of miR-21 altered the protein expression of PTEN and phosphorylated Akt (p-AKT). Conclusion: miR-21 can modulate the malignant phenotypes such as proliferation, anti-apoptosis, cell cycle progression and invasion of CRC cells by down-regulating PTEN protein expression. The results of study might improve our understanding of the regulatory mechanism of miR-21 and provide useful targets and approaches for the clinical diagnosis and therapy of CRC.
机译：> 背景/目的： 已证明MicroRNA-21（miR-21）在致癌作用中起着重要作用。然而，其在大肠癌（CRC）中的作用机理尚未完全阐明。本研究的目的是探讨miR-21的致癌作用及其分子机制。 方法： 研究了来自CRC患者和两个CRC细胞系（HCT-116和SW480）的105对配对的肿瘤和与肿瘤相邻的正常组织标本。使用蛋白质印迹分析和实时逆转录PCR（qRT-PCR）检测PTEN和miR-21的蛋白质和mRNA表达水平。此外，我们用miR-21的异位表达载体或shRNA表达载体与磷酸酶和张力蛋白同源物（PTEN）的不同组合转染CRC细胞，以分别调节miR-21和PTEN的表达水平，然后分析其的表型改变。 CRC细胞。还通过将HCT-116细胞异种移植到裸鼠中来评估肿瘤发生。 结果： 在这项研究中，我们表明，与正常组织相比，CRC中的miR-21表达明显上调。晚期肿瘤结点转移（TNM），淋巴结转移，局部浸润和较高的血清癌胚抗原（CEA）水平的患者显示出miR-21的高表达。 CRC组织和细胞中的PTEN蛋白水平与miR-21表达呈负相关。此外，用pre-miR-21转染CRC细胞可以抑制凋亡并促进裸鼠体内异种移植的细胞增殖，侵袭，细胞周期进程和生长，而miR-21特异性shRNA的转染导致相反的现象。此外，沉默或升高PTEN蛋白可以部分逆转miR-21特异的shRNA或pre-miR-21对细胞凋亡，细胞周期分布和CRC细胞侵袭的影响。此外，miR-21的过表达或敲低改变了PTEN和磷酸化Akt（p-AKT）的蛋白质表达。 结论： miR-21可通过下调PTEN蛋白表达来调节恶性表型，如增殖，抗凋亡，细胞周期进程和CRC细胞侵袭。研究结果可能会增进我们对miR-21调控机制的了解，并为CRC的临床诊断和治疗提供有用的靶点和方法。

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