Long non‑coding RNA HHIP‑AS1 inhibits lung cancer epithelial‑mesenchymal transition and stemness by regulating PCDHGA9.

Abstract

The aim of the present study was to investigate the effect of hedgehog-interacting protein antisense RNA 1 (HHIP-AS1) on epithelial-mesenchymal transition (EMT) and cellular stemness of human lung cancer cells by regulating the microRNA (miR)-153-3p/PCDHGA9 axis. Reverse transcription-quantitative PCR was used to compare the expression of HHIP-AS1 in lung cancer and adjacent normal lung tissues. In addition, the correlation of HHIP-AS1 with E-cadherin, Vimentin, N-cadherin and Twist1 was analyzed. HHIP-AS1 overexpression vector was transfected into lung cancer A549 and NCI-H1299 cell lines. Cell Counting Kit-8 and Transwell and clonogenic assays were used to detect the proliferation, invasion and clonogenesis of the lung cancer cells, respectively. The associations among HHIP-AS1, miR-153-3p and PCDHGA9 were predicted by bioinformatics analysis and verified by a dual-luciferase reporter system. The results showed that the expression of HHIP-AS1 in lung cancer tissues was significantly lower than that in normal tissues (P<0.001). HHIP-AS1 was positively correlated with E-cadherin and negatively correlated with Vimentin, N-cadherin and Twist1. HHIP-AS1 overexpression inhibited the proliferation, invasion and clonal formation of the A549 and NCI-H1299 cells. The luciferase reporter system verified that HHIP-AS1 could adsorb miR-153-3p and that PCDHGA9 was the target gene of miR-153-3p. A549 cells were transfected with HHIP-AS1 overexpression vector and miR-153-3p mimic, and the miR-153-3p mimic had a mitigating effect on HHIP-AS1 inhibition (P<0.001). In conclusion, HHIP-AS1 inhibits the EMT and stemness of lung cancer cells by regulating the miR-153-3p/PCDHGA9 axis. Thus, HHIP-AS1 may be a new potential target for lung cancer treatment.