Overexpression of lncRNA HOXA-AS2 promotes the progression of oral squamous cell carcinoma by mediating SNX5 expression

Abstract

Background Oral squamous cell carcinoma (OSCC) is one of the most common head and neck cancers. Long non-coding RNA HOXA-AS2 (lncRNA HOXA-AS2) have been extensively studied in various cancers. However, the expression and function of HOXA-AS2 in OSCC still remain unknown. The aim of this study is to investigate the roles of HOXA-AS2 in OSCC. Methods OSCC tissues and adjacent normal tissues were obtained from OSCC patients. RT-qPCR and Western blot assays were used to detect the expression of target genes in OSCC tissues or cells. Cells proliferation, migration and invasion were detected by CCK-8 and transwell assays, respectively. The target gene of HOXA-AS2 was confirmed by dual-luciferase reporter gene assay. Results We found that HOXA-AS2 expression was remarkably upregulated in OSCC tissues and cell lines. The downregulation of HOXA-AS2 inhibited cells proliferation, migration and invasion. Our bioinformatics analysis found that HOXA-AS2 can target miR-520c-3p, which was confirmed by dual-luciferase reporter gene assay. The expression of HOXA-AS2 was found to be negatively associated with miR-520c-3p in OSCC tissues. Moreover, sorting nexin 5 (SNX5), a downstream target of miR-520c-3p, was inhibited by miR-520c-3p overexpression. SNX5 was also increased in OSCC tissues and cell lines. Additionally, we found that the higher expression of SNX5 was strongly associated with the tumor grade of OSCC patients in Oncomine database. Most importantly, the knockdown of HOXA-AS2 induced cells apoptosis by promoting autophagy by regulating SNX5. Conclusion HOXA-AS2 served an oncogene and promoted OSCC progression via the miR-520c-3p/SNX5 axis. Thus, HOXA-AS2 may be a new biomarker for diagnosis and treatment of OSCC.

Characterization of SNX5 in Orange-Spotted Grouper (Epinephelus coioides) during In Vitro Viral Infection

“…Given that inhibition of autophagy and promotion of apoptosis were conducive to the persistent infection of virus [34], the present data suggested that EcSNX5 had positive regulatory roles on viral infection. In mammals, SNX5 can increase the expression of ERK 1/2 that inhibits autophagy by activating the mTOR signaling pathway [35], suggesting that EcSNX5 may also have unique way of inhibiting autophagy. Additionally, given that autophagy contributes to RGNNV replication [36], these data suggested that EcSNX5 promote virus proliferation by inhibiting autophagy.…”

Role of HOXA1-4 in the development of genetic and malignant diseases

“…In PCa, HOXA-AS2 plays a role in the regulation of cell proliferation, migration, and EMT through the miR-885-5p/KDM5B and miR-509-3p/PBX3 axes [ 165 , 166 ]. Furthermore, in OSCC, HOXA-AS2 promotes tumor progression by modulating CDK8 and SNX5, while suppressing miR-567 and miR-520c-3p, respectively [ 167 , 168 ]. Moreover, HOXA-AS2 acts as a sponge for miR-520c-3p and miR-106a to regulate TGFBR2/RELA and SCN3A, respectively, thereby enhancing tumor progression in BC [ 169 , 170 ].…”