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)
  • Received : 2018.08.30
  • Accepted : 2018.11.07
  • Published : 2019.03.31


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.


Animal model;Cell viability;Chemo-sensitivity;LncRNA MALAT1;MiR-197-3p;non-small cell lung cancer;P120-catenin

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Fig. 1. Expressions of lncRNA MALAT1 and miR-197-3p within lung cancer tissues.

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Fig. 2. The lung cancer cells were compared regarding their sensitivities to chemotherapies, including cisplatin (A), adriamycin (B), gefitinib (C) and paclitaxel (D).

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Fig. 3. Impacts of MALAT1 and miR-197-3p on the sensitivity of lung cancer cells to chemo-therapies.

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Fig. 4. The viability (A), proliferation (B), expressions of EMT-specific proteins (C) and apoptosis (D) of lung cancer cells were examined among pcDNA-MALAT1, si-MALAT1, miR-197-3p mimic, miR-197-3p inhibitor and NC groups.

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Fig. 5. The correlations among MALAT1, miR-197-3p and p120-catenin within lung cancer cells.

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Fig. 6. The viability (A), proliferation (B), expressions of EMT-specific proteins (C) and apoptosis (D) of lung cancer cells were examined among miR-NC, miR-197-3p mimic and miR-NC+si-p120-catenin groups.

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Fig. 7. Effects of MALAT1, miR-197-3p and p120-catenin on tumor formation within mice models of lung cancer.

Table 1. Primer sequences of for quantitative real-time PCR

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Table 2. Linkage of lncRNA MALAT1 and miR-197-3p expression with clinical characteristics of non-small cell lung cancer patients.

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Table 3. Impacts of MALAT1 expression, miR-197-3p expression and clinical characteristics on the survival rates of non-small cell lung cancer patients

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