Long Noncoding RNA HOXA-AS2 Promotes Papillary Thyroid Cancer Progression by Regulating miR-520c-3p/S100A4 Pathway.

BACKGROUND/AIMS: Thyroid cancer is one of the most prevalent endocrine tumors. The present study examined the effects of lncRNA HOXA cluster antisense RNA2 (HOXA-AS2) on the progression of papillary thyroid cancer (PTC), and explored the underlying molecular mechanisms.

METHODS: Quantitative real-time PCR was used to detect HOXA-AS2, miR-520c-3p and S100 calcium-binding protein A4 (S100A4) expression. Furthermore, the effects of HOXA-AS2 silencing and overexpression on cell proliferation, migration, and invasion were assessed in PTC in vitro by CCK8 and transwell assay. Furthermore, bioinformatics online programs predicted and luciferase reporter assay were used to validate the association of HOXA-AS2 and miR-520c-3p in PTC.

RESULTS: We observed that HOXA-AS2 was up-regulated in PTC tissues. In vitro experiments revealed that HOXA-AS2 knockdown significantly inhibited cell growth in PTC in vitro and in vivo. Further functional assays indicated that HOXA-AS2 significantly promoted PTC cell migration and invasion by promoting EMT. Bioinformatics online programs predicted that HOXA-AS2 sponge miR-520c-3p at 3'-UTR with complementary binding sites, which was validated using luciferase reporter assay. HOXA-AS2 could negatively regulate the expression of miR-520c-3p in PTC cells. MiR-520c-3p was down-regulated in PTC tissues, and S100A4 was predicted as a downstream target of miR-520c-3p, which was confirmed by luciferase reporter assay.

CONCLUSION: In summary, our results suggested that the HOXA-AS2/miR-520c-3p/S100A4 axis may play an important role in the regulation of PTC progression, which provides us with new insights into understanding the PTC.