LncRNA HOXA-AS2 regulates microRNA-216a-5p to promote malignant progression of non-small cell lung cancer

T.-J. Cui, G.-S. Lin, Y.-M. Dai, J.-P. Zheng, Z. Chen, Q. Chen, Y. Zheng, X. Lin

Department of Medical Oncology, Fujian Provincial Hospital, Fuzhou, China. fjslctj@163.com

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• Geriatrics

OBJECTIVE: Previous studies have shown that long non-coding RNA (lncRNA) HOXA-AS2 is a cancer-promoting gene. However, the role of HOXA-AS2 in non-small cell lung cancer (NSCLC) has not been reported. This study aims to investigate the expression characteristics of HOXA-AS2 in NSCLC and whether HOXA-AS2 can promote the malignant progression of NSCLC by regulating microRNA-216a-5p.

PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to examine the HOXA-AS2 level in 40 pairs of NSCLC tumor tissue samples and adjacent ones. Then, the relationship between HOXA-AS2 expression and clinical indicators and prognosis of NSCLC was analyzed. Meanwhile, qRT-PCR further verified the expression level of HOXA-AS2 in NSCLC cell lines. Also, HOXA-AS2 knockdown and overexpression models were constructed using lentivirus in NSCLC cell lines, and the effects of HOXA-AS2 on the biological function of NSCLC cells were analyzed using the Cell Counting Kit-8 (CCK-8), transwell migration, and cell wound healing assays. Finally, Western blotting assay and cell recovery experiment were used to explore the regulatory mechanism of HOXA-AS2 and microRNA-216a-5p in NSCLC.

RESULTS: In this experiment, qRT-PCR results revealed that HOXA-AS2 level in NSCLC tumor tissue specimens was remarkably higher than that in adjacent tissues. Compared with those with low expression of HOXA-AS2, the patients with high expression had a higher incidence of distant metastases and a lower overall survival rate. The proliferative and metastasis abilities of the cells in the HOXA-AS2 overexpression group were remarkably increased when compared with the control group, while the opposite results were observed in HOXA-AS2 silence group. Subsequently, qRT-PCR verified that microRNA-216a-5p level was remarkably decreased in NSCLC tissues and negatively correlated with HOXA-AS2 expression. In addition, the result of the cell recovery experiment and Western blotting revealed that there might be a mutual regulation between HOXA-AS2 and microRNA-216a-5p, the two of which could jointly regulate the malignant progression of NSCLC.

CONCLUSIONS: The results indicate that lncRNA HOXA-AS2 is upregulated in NSCLC and is remarkably associated with distant metastasis and poor prognosis of NSCLC patients. In addition, lncRNA HOXA-AS2 is found to be able to promote the malignant progression of NSCLC via regulating microRNA-216a-5p.

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