Long non-coding RNA MALAT1 regulates proliferation, apoptosis, migration and invasion via miR-374b-5p/SRSF7 axis in non-small cell lung cancer

J. Song, Z.-Z. Su, Q.-M. Shen

Department of Respiratory Medicine, Yantai Yuhuangding Hospital, Yantai, China. neltsf@163.com

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• Oncology

OBJECTIVE: Non-small cell lung cancer (NSCLC) is a common type of lung cancer. Long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was reported to play a tumor-promoting role in NSCLC; however, the regulatory mechanism of MALAT1 in NSCLC progression remains largely unknown.

MATERIALS AND METHODS: The expression levels of MALAT1, miR-374b-5p and SRSF7 were measured by quantitative real-time polymerase chain reaction (qRT-PCR), and the protein level of SRSF7 was detected by Western blot analysis. Cell proliferation and apoptosis were determined by cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. Cell migration and invasion were assessed by transwell assay. In addition, starBase3.0 software and dual-luciferase reporter assay were used to identify the correlations between miR-374b-5p and MALAT1 or SRSF7. Nude mouse xenograft assay was performed to explore the effects of MALAT1 on NSCLC in vivo.

RESULTS: We first observed that the levels of MALAT1 and SRSF7 were upregulated while miR-374b-5p was downregulated in NSCLC tissues; meanwhile, the expression level of MALAT1 was negatively correlated with miR-374b-5p and positively correlated with SRSF7. Both knockdown of MALAT1 and miR-374b-5p overexpression inhibited proliferation, migration and invasion and induced apoptosis in NSCLC cells. Then, we identified that miR-374b-5p was a target of MALAT1 and SRSF7 was the downstream of miR-374b-5p. In addition, overexpression of SRSF7 reversed the effects of MALAT1 knockdown on proliferation, apoptosis, migration and invasion in NSCLC cells. Finally, overexpression of MALAT1 suppressed NSCLC tumor growth in vivo.

CONCLUSIONS: Our results demonstrated that MALAT1 contributed to NSCLC progression through the MALAT1/miR-374b-5p/SRSF7 axis.

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