Hypoxia-induced microRNA-590-5p promotes colorectal cancer progression by modulating matrix metalloproteinase activity. (1st March 2018)

• Record Type: Journal Article
• Authors: Kim, Chan Woo; Oh, Eun-Taex; Kim, Joon Mee; Park, Jin-Seok; Lee, Don Haeng; Lee, Jae-Seon; Kim, Kyung Keun; Park, Heon Joo
• Is Part Of: Cancer letters. Volume 416(2018)
• Page Start: 31
• Page End: 41
• Publication Date: 2018-03-01
• Subjects: Colorectal cancer -- microRNA -- Hypoxia -- Tumor progression -- Metastasis; CRC colorectal cancer -- HIF hypoxia-inducible factor -- miRNA microRNA -- pPCR quantitative polymerase chain reaction -- RECK reversion-inducing cysteine-rich protein with kazal motifs -- MMP matrix metalloproteinase -- TCGA the cancer genome atlas -- 3′-UTR 3′-untranslated region; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2017.12.018
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: Hypoxia leads to cancer progression and promotes the metastatic potential of cancer cells. MicroRNAs (miRNAs) are small non-coding RNA that have emerged as key players involved in cancer development and progression. Hypoxia alters a set of hypoxia-mediated miRNAs expression during tumor development and it may function as oncogenes or tumor-suppressors. However, the roles and molecular mechanisms of hypoxia-regulatory miRNAs in colorectal cancer (CRC) progression remain poorly understood. Here we firstly identified miR-590-5p as hypoxia-sensitive miRNAs which was upregulated in colon cancer cells under hypoxia. Hypoxia-induced miR-590-5p suppressed the expression of RECK, in turn, promoting cell invasiveness and migratory abilities via activation of matrix metalloproteinases (MMPs) and filopodia protrusion in vitro . Inhibition of miR-590-5p suppressed tumor growth and metastasis in mouse xenograft and CRC liver metastasis models via inhibition of MMPs activity. Clinical analysis revealed higher miR-590-5p expression in CRC, compared to normal specimens. Furthermore, miR-590-5p expression was significantly increased in liver metastasis as compared to their matched primary CRC. Taken together, our findings provide the first evidence that miR-590-5p may have potential as a therapeutic target for CRC patients with metastasis. Highlights: MiR-590-5p is hypoxia-sensitive miRNAs which was upregulated in colon cancer cells under hypoxia. Hypoxia-induced miR-590-5p enhanced matrix metalloproteinase activity by targeting RECK. Inhibition of miR-590-5p suppressed tumor growth and metastasis in vivo . miR-590-5p is more upregulated in human liver metastasis tissues, compared to primary CRC. Targeting of hypoxia-induced miR-590-5p may provide an effective therapeutic approach to inhibit CRC progression.