Effects of MALAT1 on proliferation and apo- ptosis of human non-small cell lung cancer A549 cells in vitro and tumor xenograft growth in vivo by modulating autophagy
Affiliations: [a] Thoracic Surgery Department, 1st Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong, China | [b] Colorectal Surgery Department, 1st Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong, China | [c] Department of Anaesthesiology, 1st Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong, China | [d] Physical Exam. Center, The Eastern Hospital of 1st Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510700, Guangdong, China
Correspondence:
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Corresponding author: Jun Ma, Thoracic Surgery Department, 1
Abstract: OBJECTIVE: To explore the ability of MALAT1 to influence non-small cell lung cancer (NSCLC) A549 cells in vitro and tumor xenograft growth in vivo by modulating autophagy. METHODS:LncRNA MALAT-1 in normal HBE cells and human NSCLC cells was measured. A549 cells were treated with si-MALAT-1, negative control and si-MALAT-1 + rapamycin. The mRNA levels of MALAT-1, P62 and LC3 was determined by the qRT-PCR and the protein levels of autophagy-related proteins by the western blotting. The CCK8 assay was performed for cell proliferation, the scratch test for cell migration, the Transwell assay for cell invasion, and the flow cytometry for cell cycle and apoptosis. Tumor xenograft in nude mice is performed to test tumorigenesis of the transfected A549 cells. RESULTS:The expression level of MALAT-1 in A549, SPC-A-1 and NCI-H460 cells was increased compared to HBE cells. And A549 with a high expression level of MALAT-1 were selected for cell transfection. si-MALAT-1 decreased cell proliferation, migration, invasion, and LC3-II/LC3-I ratio, reduced cell cycle progression, and increased cell apoptosis and P62 protein expression. No significant difference was found between A549 cells and A549 cells transfected with si-MALAT-1 + RAPA, A549 cells transfected with NC and A549 cells transfected with si-MALAT-1 + RAPA. Nude mice injected with A549 cells transfected with si-MALAT-1 had smallest tumor on size and weight among other nude mice. CONCLUSION: Downregulation of MALAT1 may promote apoptosis and suppress proliferation, migration and invasion of human NSCLC A549 cells by inhibiting autophagy, thereby suppressing the development of NSCLC.
