Abstract
Objective: Long non-coding RNAs (lncRNAs) are critical to colorectal cancer (CRC) progression. In the current study, the objective was the exploration of the role played by lncRNA MIR4435-2HG in CRC proliferation and metastasis.Methods: lncRNA MIR4435-2HG expression and its association with CRC were analyzed using database and clinical specimens. The influences exerted by MIR4435-2HG on cell proliferating process, invading process, and migrating process of CRC were identified after MIR4435-2HG knockdown. The influences exerted by MIR4435-2HG on tumor growth and metastasis were assessed in vivo. The underlying mechanistic associations between MIR4435-2HG, microRNA miR-206, and the transcription factor Yes-associated protein 1 (YAP1) were assessed using bioinformatics and a luciferase reporter gene assay.Results: MIR4435-2HG was highly expressed in CRC tissue in contrast with that in regular tissues and displayed relations to poor prognosis. MIR4435-2HG knockdown could suppress CRC cell proliferation, invasion, and migration. Moreover, MIR4435-2HG knockdown inhibited CRC growth and liver metastasis in vitro. We found MIR4435-2HG knockdown reduced YAP1, CTGF, AREG, vimentin, Snail, Slug, and Twist expression but enhanced E-cadherin expression. Functionally, MIR4435-2HG acted as a competing endogenous RNA (ceRNA) to upregulate YAP1 by sponging miR-206.Conclusions: MIR4435-2HG promoted CRC growth and metastasis through miR-206/YAP1 axis and is likely to play prognostic marker roles and be therapeutically targeted in CRC.
Highlights
Colorectal cancer (CRC) refers to a top three newly identified and deadliest forms of cancer in many nations (e.g., U.S.) [1]
We explored the role of MIR4435-2HG in CRC proliferation and metastasis and proved that MIR4435-2HG regulated proliferation and metastasis of CRC via miR-206-Yes-related protein 1 (YAP1) axis
Complete data was available for Abbreviations: lncRNAs, Long non-coding RNAs; CRC, colorectal cancer; TCGA, The Cancer Genome Atlas; YAP1, Yes-associated protein 1; ceRNA, competing endogenous RNA; EMT, epithelial-mesenchymal transition
Summary
Colorectal cancer (CRC) refers to a top three newly identified and deadliest forms of cancer in many nations (e.g., U.S.) [1]. Great progress has been made in recent years in treating patients with CRC using radiotherapy, chemotherapy, surgical treatment, and immunotherapy [2], the prognostic process of CRC cases in late stage continues to be not favorable [3]. Identifying biomarkers of metastasis and therapeutic targets in CRC would facilitate favorable prognoses for patients with CRC. Recent studies have shown lncRNA MIR4435-2HG displays relations to cancer progression in triple-negative breast cancer [9] and osteosarcoma [10]. LncRNA MIR4435-2HG expression promotes tumor proliferation and lymph node transfer in lung cancer [11] and is a diagnosis- and prognosis-related biomarker in the plasma of gastric carcinoma cases [12]. MIR4435-2HG clearly displays relations to the production and development of several cancers
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