Long Intergenic Noncoding RNA 00261 Acts as a Tumor Suppressor in Non-Small Cell Lung Cancer via Regulating miR-105/FHL1 Axis

J Cancer. 2019 Oct 19;10(25):6414-6421. doi: 10.7150/jca.32251. eCollection 2019.

Abstract

Purpose: Long noncoding RNAs (lncRNAs) have recently received more attention for their roles in tumor progression. LINC00261 was studied in this research to identify how it affects the progression of non-small cell lung cancer (NSCLC). Methods: Firstly, the expression of LINC00261 in NSCLC cells and paired samples of NSCLC tissue was detected by RT-qPCR. Then, the associations between LINC00261 expression level and clinicopathological characteristics were evaluated. Furthermore, functional assays of cell proliferation, colony formation and transwell, as well as western blot assay, luciferase assay and RNA immunoprecipitation (RIP) assay were conducted. Afterwards, the effects of LINC00261 expression on NSCLC formation and growing were confirmed by in vivo models. Results: As results, expression of LINC00261 was significantly down-regulated in tumor samples than that in normal samples, which was correlated with the lymphatic metastasis, tumor size, tumor stage as well as patient survival time. Knockdown of LINC00261 inhibited tumor growth and invasion ability in vitro. In addition, miR-105 was identified as a direct target of LINC00261 via mechanism experiments and its expression in tumor tissues negatively correlated to LINC00261 expression. Further experiments found that Four and expression of Half LIM domains 1 (FHL1) was negatively correlated with miR-105 but positively with LINC00261. Moreover, in vivo assays verified the overexpression of LINC00261 could suppress formation of NSCLC and regulate the expression of miR-105/FHL1 axis. Conclusions: These results indicate that LINC00261 could suppress metastasis and proliferation of NSCLC via suppressing miR-105/FHL1 axis, which may offer a new vision for interpreting the mechanism of NSCLC development.

Keywords: FHL1; LINC00261; Non-small cell lung cancer; miR-105.