Si-MALAT1 attenuates thymic cancer cell proliferation and promotes apoptosis via the miR-145-5p/HMGA2 pathway.

Abstract

Metastasis-associated-lung-adenocarcinoma-transcript-1 (MALAT1) is a long non-coding RNA that is considered a potential tumor marker. The present study aimed to investigate the effect and mechanism of MALAT1 on cell proliferation and apoptosis in thymic cancer cells. IU-TAB-1, A549, HCT-116 and 293T cells were screened by reverse transcription-quantitative PCR to assess high-mobility group AT-hook 2 (HMGA2) expression in various types of cancer cells and were transfected with small interfering (si)RNA targeting MALAT1 (si-MALAT1). Cell proliferation was evaluated by Cell Counting Kit-8 assay. Cell apoptosis and cell cycle were examined using flow cytometry. The protein expression of cyclin D1, cyclin E, Bax, Bcl-2 and HMGA2 was determined by western blot analysis, while the associations between MALAT1 and microRNA (miR)-145-5p and between HMGA2 and miR-145-5p were determined by luciferase reporter assay. Among the four cell lines evaluated, IU-TAB-1 showed the highest expression of MALAT1; thus, IU-TAB-1 cells were selected for subsequent experiments. Compared with the findings in the control group, si-MALAT1 significantly decreased the cell proliferation of IU-TAB-1 cells, whereas the apoptosis levels and number of cells in G2 phase were increased. The protein expression levels of cyclin D1, cyclin E, Bcl-2 and HMGA2 were significantly decreased in the si-MALAT1 group compared with those in the control group, while Bax levels were significantly increased. After treatment with si-MALAT1 in combination with miR-145-5p mimics or inhibitors, cell proliferation and apoptosis were respectively enhanced and inhibited in IU-TAB-1 cells. miR-145-5p inhibited the luciferase activity of IU-TAB-1 cells transfected with the MALAT1 or HMGA2 3′ untranslated region. In conclusion, si-MALAT1 significantly attenuated cell proliferation and apoptosis via the miR-145-5p/HMGA2 pathway in thymic cancer cells.