Circular RNA La-Related Protein 4 Inhibits Non-Small Cell Lung Cancer Cell Proliferation While Promotes Apoptosis Through Sponging microRNA-21-5p.

Abstract

Background: This study aimed to investigate the function of circular RNA La-related protein 4 (circ-LARP4) on non-small cell lung cancer (NSCLC) progression. Materials and Methods: Circ-LARP4 overexpression and circ-LARP4 short hairpin RNA (shRNA) plasmids were transfected into NCI-H1650 cells and NCI-H1299 cells respectively. In rescue experiment, microRNA (miR)-21-5p overexpression and miR-21-5p shRNA plasmids were transfected into circ-LARP4 overexpression-treated NCI-H1650 cells and circ-LARP4 knockdown-treated NCI-H1650 cells, respectively. Circ-LARP4 and miR-21-5p expression levels were detected by reverse transcription-quantitative polymerase chain reaction. Cell proliferation and apoptosis were investigated by cell counting kit-8 assay and annexin V/propidium iodide assay. The interaction between circ-LARP4 and miR-21-5p was further explored by luciferase reporter assay. Results: Circ-LARP4 expression was decreased in NSCLC cell lines (including NCI-H1299, NCI-H522, NCI-H23, NCI-H358, and NCI-H1650) compared with human normal lung epithelial cell line. Circ-LARP4 overexpression inhibited cell proliferation while promoted apoptosis in NCI-H1650 cells, whereas circ-LARP4 knockdown increased cell proliferation while decreased apoptosis in NCI-H1299 cells. Meanwhile, miR-21-5p was negatively regulated by circ-LARP4, whereas circ-LARP4 was not affected by miR-21-5p in NCI-H1650 and NCI-H1299 cells. In rescue experiment, miR-21-5p overexpression attenuated the effect of circ-LARP4 overexpression on decreasing cell proliferation and increasing apoptosis in NCI-H1650 cells, whereas miR-21-5p knockdown attenuated the effect of circ-LARP4 knockdown on promoting cell proliferation and suppressing apoptosis in NCI-H1299 cells. Further luciferase reporter assay revealed that circ-LARP4 could directly bind to miR-21-5p. Conclusions: Circ-LARP4 is decreased and suppresses cell proliferation while promoted apoptosis by sponging miR-21-5p in NSCLC.