Promotion of BZW2 by LINC00174 through miR-4500 inhibition enhances proliferation and apoptosis evasion in laryngeal pap
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PRIMARY RESEARCH
Cancer Cell International Open Access
Promotion of BZW2 by LINC00174 through miR‑4500 inhibition enhances proliferation and apoptosis evasion in laryngeal papilloma Jiajia Liu, Tao Yang, Ying Zhang and Shuhui Wang*
Abstract Background: We aimed to explore the roles of basic leucine zipper and W2 domains (BZW) 2 in the human papillomavirus-infected laryngeal papillomatosis. Methods: In the present study, BZW 2 knockdown and overexpressed cell lines were constructed. CCK-8 and colony formation assays were used to determine cell proliferation. Caspase-3 activity and nucleosomes fragmentation assays were used to determine cell apoptosis. qRT-PCR and Western blot were employed to evaluate the mRNA and protein levels of target genes, respectively. Luciferase and biotin-coupled miRNA pulldown assays were used to examine the interactions between mRNA and mRNA. Results: We observed the levels of BZW2 were up-regulated in the laryngeal papilloma (LP) tissues as compared with adjacent tissues. The knockdown of BZW2 significantly inhibited cell proliferation and promoted cell apoptosis in the LP cells. Additionally, we identified the expressions of BZW2 negatively regulated by miR-4500. Luciferase and biotincoupled miRNA pulldown assays demonstrated that LINC00174 competed with the BZW2 for binding with miR-4500. Moreover, the results showed that LINC00174/miR-4500/BZW2 axis regulated cell proliferation and apoptosis. Conclusion: Our results demonstrated that the regulation of LINC00174/miR-4500/BZW2 axis might be used as an effective strategy for treatment of human papillomavirus-infected laryngeal papillomatosis. Keywords: Laryngeal papillomatosis, BZW2, miR-4500, LINC00174, Apoptosis Background Laryngeal papillomatosis (LP) is a rare disease caused by human papillomavirus (HPV) infection. As a benign squamous epithelial tumor occurred in the larynx, the LP is divided into juvenile and adult types based on age [1, 2]. Although its incidence is low, it is one of the major risk factors for children hoarseness. Additionally, the occurrence of LP also induces short of breath, chronic *Correspondence: [email protected] Department of Otolaryngology‑Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China
cough, and even asthma. When the LP spreads, it is difficult to remove all tumor tissues, thereby leading to its recurrence [2]. Besides, the recurrence of LP leads to its resistance to cell apoptosis [3]. Therefore, it is of great importance to understand the mechanisms underlying the occurrence and development of LP. MicroRNAs (miRNAs) have been implicated to play an important role in various biological processes including cell migration, proliferation, invasion and apoptosis [4–6]. Since the discovery of miRNAs, a growing body of evidences support that they are associated with a series of diseases including
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