Abstract:

Objective To investigate the impacts of LncRNA SNHG15 on cisplatin（DDP）sensitivity and epithelial⁃mesenchymal transition of non⁃small cell lung cancer（NSCLC）cells and the role of miR⁃483⁃3p/DNA damage⁃induced transcript 4（DDIT4）axis. Methods NSCLC cells（A549）and NSCLC drug⁃resistant cells（A549/ DDP）were cultured in vitro，the IC50 of the two cells to DDP and the mRNA and protein expression of LncRNA SN⁃ HG15，miR⁃483⁃3p and DDIT4 in the two cells were detected.A549/DDP cells were randomly divided into A549/ DDP group，si NC group，si SNHG15 group，si SNHG15+inhibitor NC group，si SNHG15+miR⁃483⁃3p inhibitor group，si SNHG15+miR⁃483⁃3p inhibitor+si NC group，and si SNHG15+miR⁃483⁃3p inhibitor+si DDIT4 group. Western blot was used to detect the changes of E⁃cad，N⁃cad and DDIT4 protein expression in each group anddual⁃ luciferase reporter assay was used to verify the targeting relationship of miR ⁃ 483⁃3p with LncRNA SNHG15 and DDIT4. Results Compared with A549 cells，the IC50，LncRNA SNHG15，DDIT4 mRNA and protein of DDP in A549/DDP cells increased，and the miR⁃483⁃3p level decreased（P < 0.05）. In A549/DDP group，intercellular adhesion was significantly destroyed. The cells of si SNHG15 group and si SNHG15 + miR ⁃ 483 ⁃ 3p inhibitor + si DDIT4 group were relatively closely arranged，showing epithelial characteristics. The cells in the si SNHG15+miR⁃ 483⁃3p inhibitor group were loosely arranged and diffused as compared with the si SNHG15 group. Compared with A549/DDP group，the inhibition rate of A549/DDP cell proliferation and the expression of E ⁃ cad in si SNHG15group increased，while the number of invasive cells，the number of migrating cells，the expression of N⁃cad and DDIT4 decreased（P < 0.05）. Compared with the si SNHG15 group，the proliferation inhibition rate and E ⁃cad expression of A549/DDP cells in the si SNHG15+miR⁃483⁃3p inhibitor group decreased，and the number of invasive cells，the number of migrating cells，N⁃cad and DDIT4 expression increased（P < 0.05）. Conclusion Silencing the expression of SNHG15 in A549/DDP cells can inhibit the proliferation，invasion，migration and EMT of A549/ DDP cells，and reduce the drug resistance of A549/DDP cells to DDP by regulating miR⁃483⁃3p/DDIT4.

Key words:

"> LncRNA SNHG15, miR?483?3p, DNA damage?inducible transcript 4, non?small cell lung cancer, cisplatin, epithelial?mesenchymal transition