Wen Liqiang, Li Yingru, Jiang Zhipeng, Zhang Yuchao, Yang Bin, Han Fanghai
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.
Oncol Rep. 2017 Jun;37(6):3415-3422. doi: 10.3892/or.2017.5611. Epub 2017 Apr 28.
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.
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。