MALAT1 enhances gemcitabine resistance in non-small cell lung cancer cells by directly affecting miR-27a-5p/PBOV1 axis

Objective: MALAT1 has been implicated in tumor progression. But the mechanism and role underlying MALAT1 in non-small cell lung cancer (NSCLC) cell resistance to gemcitabine (GEM) remain rarely understood.Methods: Through bioinformatics analysis, we predicted MALAT1/miR-27a-5p/PBOV1 regulatory axis and constructed GEM resistant A549/GEM cell line, and A549 was the parent cell line. qRT-PCR was utilized to assess MALAT1, miR-27a-5p and PBOV1 expression in A549 and A549/GEM cells. MTT method and colony formation assay were utilized to measure cell viability and cell proliferation. Flow cytometry was conducted to assess cell cycle and cell apoptosis. Wound healing and Transwell assays were conducted to measure cell migratory and invasive potentials. Dual-luciferase reporter gene assay and RNA immunoprecipitation were utilized to identify the targeted relationship between MALAT1 and miR-27a-5p, and the former assay was also utilized to determine the targeted relationship between miR-27a-5p and PBOV1. The impacts of MALAT1/miR-27a-5p/PBOV1 on tumor growth and GEM resistance of NSCLC cells in vivo were validated by using the tumor xenograft model. Results: MALAT1 was observed to be highly expressed in tissues and cells of GEM resistant patients. Forced level of MALAT1 could markedly enhance A549 cell resistance to GEM, but this impact could be weakened by silencing MALAT1. MALAT1 downregulated miR-27a-5p level. PBOV1 was the target of miR-27a-5p and could significantly enhance GEM resistance of NSCLC cell. MALAT1 facilitated tumor growth in vivo via targeting miR-27a-5p/PBOV1 and enhanced resistance of NSCLC cells to GEM.Conclusion: MALAT1/miR-27a-5p/PBOV1 axis was implicated in NSCLC cell resistance to GEM. We deepened our understanding about how MALAT1 enhanced NSCLC cell resistance to GEM and provided development of therapeutic strategy for NSCLC with a possible target.

Automated summary

MALAT1/miR-27a-5p/PBOV1 axis is implicated in NSCLC cell resistance to GEM. MALAT1 enhances NSCLC cell resistance to GEM by downregulating miR-27a-5p and targeting PBOV1, providing a potential therapeutic strategy for NSCLC.