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http://dx.doi.org/10.14348/molcells.2019.2364

LncRNA MALAT1 Depressed Chemo-Sensitivity of NSCLC Cells through Directly Functioning on miR-197-3p/p120 Catenin Axis  

Yang, Tian (Division of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University)
Li, Hong (Division of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University)
Chen, Tianjun (Division of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University)
Ren, Hui (Division of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University)
Shi, Puyu (Division of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University)
Chen, Mingwei (Division of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University)
Abstract
This study was aimed to explore if lncRNA MALAT1 would modify chemo-resistance of non-small cell lung cancer (NSCLC) cells by regulating miR-197-3p and p120 catenin (p120-ctn). Within this investigation, we totally recruited 326 lung cancer patients, and purchased 4 NSCLC cell lines of A549, H1299, SPC-A-1 and H460. Moreover, cisplatin, adriamycin, gefitinib and paclitaxel were arranged as chemotherapies, and half maximal inhibitory concentration (IC50) values were calculated to evaluate the chemo-resistance of the cells. Furthermore, mice models of NSCLC were also established to assess the impacts of MALAT1, miR-197-3p and p120-ctn on tumor growth. Our results indicated that MALAT1 and miR-197-3p were both over-expressed within NSCLC tissues and cells, when compared with normal tissues and cells (P < 0.05). The A549, H460, SPC-A-1 and SPC-A-1 displayed maximum resistances to cisplatin ($IC50=15.70{\mu}g/ml$), adriamycin ($IC50=5.58{\mu}g/ml$), gefitinib ($96.82{\mu}mol/L$) and paclitaxel (141.97 nmol/L). Over-expression of MALAT1 and miR-197-3p, or under-expression of p120-ctn were associated with promoted viability and growth of the cancer cells (P < 0.05), and they could significantly strengthen the chemo-resistance of cancer cells (P < 0.05). MALAT1 Wt or p120-ctn Wt co-transfected with miR-197-3p mimic was observed with significantly reduced luciferase activity within NSCLC cells (P < 0.05). Finally, the NSCLC mice models were observed with larger tumor size and weight under circumstances of over-expressed MALAT1 and miR-197-3p, or under-expressed p120-ctn (P < 0.05). In conclusion, MALAT1 could alter chemo-resistance of NSCLC cells by targeting miR-197-3p and regulating p120-ctn expression, which might assist in improvement of chemo-therapies for NSCLC.
Keywords
Animal model; Cell viability; Chemo-sensitivity; LncRNA MALAT1; MiR-197-3p; non-small cell lung cancer; P120-catenin;
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