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miR-944通过靶向结直肠癌中的MACC1抑制细胞迁移和侵袭。

miR-944 inhibits cell migration and invasion by targeting MACC1 in colorectal cancer.

作者信息

Wen Liqiang, Li Yingru, Jiang Zhipeng, Zhang Yuchao, Yang Bin, Han Fanghai

机构信息

Department of Gastrointestinal Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, P.R. China.

Department of Gastroenterology, Hernia and Abdominal Wall Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510655, P.R. China.

出版信息

Oncol Rep. 2017 Jun;37(6):3415-3422. doi: 10.3892/or.2017.5611. Epub 2017 Apr 28.

Abstract

Dysfunction of microRNAs (miRNAs) is strongly proved to participate in the pathogenesis and tumorigenicity of colorectal cancer (CRC). miR-944 was reported to play either oncogenic or tumor suppressive roles in human cancers. A recent study reported that the levels of miR-944 in recurrent CRC patients were evidently lower than that in non-recurrent cases, suggesting that miR-944 may function as a tumor suppressive miRNA in CRC. Yet, the clinical value and biological function of miR-944 remain rarely known in CRC. In the present study, we present that miR-944 level in CRC tissues is notably reduced compared to matched non-cancerous specimens. Its decreased level is evidently correlated with malignant clinical parameters and poor prognosis of CRC patients. Accordingly, the levels of miR-944 were obviously downregulated in CRC cells. Ectopic expression of miR-944 in CRC cells prominently inhibits the migration and invasion of tumor cells, while miR-944 knockdown increased these effects of CRC cells. Mechanically, miR-944 negatively regulated the metastasis-associated in colon cancer-1 (MACC1) abundance in CRC cells. Herein, MACC1 was found to be a downstream molecule of miR-944 in CRC. An inversely correlation between miR-944 and MACC1 was confirmed in CRC specimens. Furthermore, restoration of MACC1 expression could abrogate the anti-metastatic effects of miR-944 on CRC cells with enhanced cell migration and invasion. MACC1/Met/AKT signaling may be implicated with the function of miR-944 in CRC cells. Altogether, miR-944 potentially act as a prognostic predictor and a drug-target for CRC patients.

摘要

微小RNA(miRNA)功能障碍已被有力证明参与了结直肠癌(CRC)的发病机制和肿瘤发生过程。据报道,miR-944在人类癌症中发挥致癌或抑癌作用。最近一项研究报告称,复发性CRC患者中miR-944的水平明显低于非复发性患者,这表明miR-944在CRC中可能作为一种抑癌miRNA发挥作用。然而,miR-944在CRC中的临床价值和生物学功能仍鲜为人知。在本研究中,我们发现与配对的非癌组织标本相比,CRC组织中miR-944水平显著降低。其水平降低与CRC患者的恶性临床参数和不良预后明显相关。因此,CRC细胞中miR-944的水平明显下调。在CRC细胞中异位表达miR-944可显著抑制肿瘤细胞的迁移和侵袭,而敲低miR-944则增强了CRC细胞的这些作用。从机制上讲,miR-944在CRC细胞中负向调节结肠癌转移相关蛋白1(MACC1)的丰度。在此,发现MACC1是CRC中miR-944的下游分子。在CRC标本中证实了miR-944与MACC1之间呈负相关。此外,恢复MACC1表达可消除miR-944对CRC细胞的抗转移作用,增强细胞迁移和侵袭。MACC1/Met/AKT信号通路可能与miR-944在CRC细胞中的功能有关。总之,miR-944可能作为CRC患者的预后预测指标和药物靶点。

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