A miR-124/ITGA3 axis contributes to colorectal cancer metastasis by regulating anoikis susceptibility

Metastasis is the major cause for the death of patients with colorectal cancer (CRC). Anoikis resistance enhances the survival of cancer cells during systemic circulation, thereby facilitating secondary tumor formation in distant organs. miR-124 is a pleiotropically tumor suppressive small non-codin...

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Veröffentlicht in:Biochemical and biophysical research communications 2018-06, Vol.501 (3), p.758-764
Hauptverfasser: Sa, Ke-di, Zhang, Xiang, Li, Xiao-fei, Gu, Zhong-ping, Yang, An-gang, Zhang, Rui, Li, Ji-peng, Sun, Jian-yong
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Sprache:eng
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Zusammenfassung:Metastasis is the major cause for the death of patients with colorectal cancer (CRC). Anoikis resistance enhances the survival of cancer cells during systemic circulation, thereby facilitating secondary tumor formation in distant organs. miR-124 is a pleiotropically tumor suppressive small non-coding molecule. However, its role and mechanism in the regulation of cancer cell anoikis are still unknown. Here, we found that overexpression of miR-124 promotes anoikis of CRC cells in vitro and in vivo. In silico analysis and the experimental evidence supported that ITGA3 is a bona fide target of miR-124. Moreover, we identifies that ITGA3 plays a critical role in the regulation of anoikis sensitivity in CRC cells. Finally, our analysis in TCGA datasets demonstrates that high levels of ITGA3 are closely associated with poor prognosis in CRC patients. Collectively, we establish a functional link between miR-124 and anoikis susceptibility and provide that a miR-124/ITGA3 axis could be a potential target for the treatment of metastatic CRC. •Overexpression of miR-124 promotes CRC cell anoikis in vitro and in vivo.•ITGA3 is a novel target of miR-124 in CRC cells.•Silencing ITGA3 recapitulates the effect of miR-124 on anoikis sensitivity in CRC cells in vitro and in vivo.•High levels of ITGA3 are associated with poor prognosis in CRC patients.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2018.05.062