lncRNA LINC00460 promoted colorectal cancer cells metastasis via miR-939-5p sponging

Cancer Manag Res. 2019 Feb 22;11:1779-1789. doi: 10.2147/CMAR.S192452. eCollection 2019.


Background: lncRNAs are widely involved in multiple malignancies including colorectal cancer (CRC). The expression and function of long intergenic non-protein coding RNA 460 (LINC00460) in CRC remains obscure.

Methods: In the present study, quantitative real-time PCR assays were applied to detect the expression changes of LINC00460 and microRNA-939-5p (miR-939-5p) in CRC tissue specimens and cell lines. Western blot assays were used to measure the changes of LIMK2. Bioinformatics analysis, luciferase assays, and RNA pull-down assays were applied to determine the targeting binding effect between LINC00460 and miR-939-5p as well as LIMK2 and miR-939-5p. Transwell assays were used to evaluate the metastatic ability changes of CRC line HT29 and LOVO cells.

Results: We found that LINC00460 was upregulated and closely correlated to clinicopathological features and poor prognosis of patients with CRC. Functionally, we elucidated that LINC00460 promoted metastasis in CRC cell lines HT29 and LOVO. Further, we showed that LIMK2 was a downstream effector in the LINC00460-induced promotion of metastasis in CRC cells HT29 and LOVO. Through online bioinformatics analysis, LINC00460 and LIMK2 were demonstrated to share similar microRNA response elements for miR-939-5p. Then, LINC00460 and LIMK2 were verified to be the targets of miR-939-5p via a luciferase assay and an RNA pull-down assay. Also, miR-939-5p was showed to suppress metastasis by targeting of LIMK2. Lastly, we revealed that LINC00460 promoted LIMK2-mediated metastasis via miR-939-5p sponging in CRC cells HT29 and LOVO.

Conclusion: The findings of this study showed that LINC00460 works as an oncogene in CRC and promoted CRC cell metastasis via regulation of miR-939-3p/LIMK2 axial. The present study might provide a new target in treating CRC.

Keywords: LINC00460; ceRNA; colorectal cancer; metastasis; miR-939-5p.