LncNORAD interference inhibits tumor growth and lung cancer cell proliferation, invasion and migration by down-regulating CXCR4 to suppress RhoA/ROCK signaling pathway

Y. Wu, Q.-W. Shen, Y.-X. Niu, X.-Y. Chen, H.-W. Liu, X.-Y. Shen

Department of Thoracic Surgery, Shanghai Key Laboratory of Clinical Geriatric Medicine, HuaDong Hospital, FuDan University, Shanghai, China. Shenxy2019@yeat.net

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• Oncology

OBJECTIVE: Non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer, with an unfavorable prognosis of 5-year survival rates. It is of great clinical significance to further search for more efficacious and novel targets for diagnosis and therapeutic strategies. This study aimed at clarifying the role of long non-coding RNA (lncRNA) NORAD in proliferation, invasion and migration and tumor growth of NSCLC.

MATERIALS AND METHODS: In this study, mRNA levels of lncRNA NORAD were examined by RT-PCR. CCK-8 assay was applied to test cell viability. Furthermore, wound healing assay and transwell assay were performed to detect the migration and invasion of A549 cells, respectively. Immunohistochemistry was applied to assess the levels of CXC chemokine receptor (CXCR) 4 and CXC chemokine ligand (CXCL) 12. Mice models of NSCLC in vivo were exploited to further examine the potential role of NORAD in tumor growth. Key proteins related to Ras homolog gene family member A (RhoA) GTPase/Rho-associated kinase (RhoA/ROCK) pathway were determined by Western blot.

RESULTS: NORAD has elevated the levels in NSCLC tissues and cells. NORAD interference dramatically inhibited tumor growth and suppressed A549 cell proliferation, migration and invasion by downregulating CXCR4 and CXCL12 expression. RhoA/ROCK signaling pathway was activated in NSCLC.

CONCLUSIONS: This study revealed that the downregulation of lncRNA NORAD could slow down the progression of NSCLC by regulating CXCR4 and RhoA/ROCK signaling pathway.

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