Oncotarget

Research Papers:

LncRNA CHRF-induced miR-489 loss promotes metastasis of colorectal cancer via TWIST1/EMT signaling pathway

Youmao Tao, Tao Han, Tao Zhang, Chong Ma and Caixia Sun _

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Oncotarget. 2017; 8:36410-36422. https://doi.org/10.18632/oncotarget.16850

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Abstract

Youmao Tao1, Tao Han1, Tao Zhang1, Chong Ma1, Caixia Sun1

1Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, China

Correspondence to:

Caixia Sun, email: scx_cjuh@163.com

Keywords: LncRNA CHRF, miR-489, TWIST1/EMT, metastasis, CRC

Received: March 10, 2017     Accepted: March 28, 2017     Published: April 05, 2017

ABSTRACT

microRNA-489 (miR-489) is a novel cancer-related miRNAs and functions as a tumor suppressor in human cancers. While, the clinical significance of miR-489 and its role in colorectal cancer (CRC) remain rarely known. Here, we found that the levels of miR-489 in CRC tissues were significantly lower than those in matched tumor-adjacent tissues. Furthermore, decreased levels of miR-489 also observed in CRC cell lines compared to HIEC cells. Clinicopathological analysis revealed that miR-489 underexpression was positively correlated with advanced pT stage, pN stage and AJCC stage. Moreover, miR-489 low expressing CRC patients showed a obvious shorter survival. Functionally, miR-489 restoration inhibited cell migration and invasion as well as epithelial-mesenchymal transition (EMT) in HCT116 cells, while miR-489 loss facilitated these cellular processes in SW480 cells. In vivo experiments revealed that miR-489 overexpression reduced the number of metastatic nodules in nude mice liver. Notably, TWIST1 was recognized as a direct downstream target of miR-489 in CRC cells. Interestingly, TWIST1 restoration abrogated the effects of miR-489 on CRC cells with enhanced cell migration, invasion and EMT process. Furthermore, overexpression of long noncoding RNA cardiac hypertrophy-related factor (lncRNA CHRF) was inversely correlated with miR-489 expression in CRC tissues. CHRF knockdown increased the expression of miR-489 and suppressed EMT events of HCT116 cells, while CHRF overexpression showed opposite effects on miR-489 expression and EMT in SW480 cells. Taken together, this work support the first evidence that lncRNA CHRF-induced miR-489 loss facilitates metastasis and EMT process of CRC cells probably via TWIST1/EMT signaling pathway.


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