Upregulation of the long non-coding RNA FOXD2-AS1 is correlated with tumor progression and metastasis in papillary thyroid cancer

Background: Mounting evidence has shown that long non-coding RNAs (lncRNAs) play critical regulation roles in the progression of various cancers. However, the biological role and clinical value of lncRNA FOXD2-AS1 in papillary thyroid cancer (PTC) remain to be elucidated.

Methods: The expression of FOXD2-AS1 in PTC tissues and cell lines was evaluated by RT-qPCR and in situ hybridization. The association between FOXD2-AS1 expression levels and clinicopathologic features was analyzed through tissue microarray. The biological function of FOXD2-AS1 in PTC cells was determined both in vitro through CCK-8, EdU staining, colony formation and cell invasion assays and in vivo through a xenograft tumor model. Functional and pathway enrichment analysis were also conducted to analyze the molecular mechanism.

Results: FOXD2-AS1 was significantly upregulated in PTC tissues, and high FOXD2-AS1 expression was positively associated with malignant potential factors in PTC patients. In addition, high level of FOXD2-AS1 expression was an unfavorable independent prognostic biomarker for patients with PTC. Moreover, we found that knockdown of FOXD2-AS1 could effectively inhibit PTC cell proliferation and invasion in vitro and suppress tumor growth of PTC in vivo. Bioinformatics analysis indicated that activation of cell cycle and apoptosis pathways might be involved in the oncogenic function of FOXD2-AS1 in PTC. Moreover, we demonstrated that FOXD2-AS1 directly interacted with miR-185-5p as miRNA sponge and overexpression of FOXD2-AS1 partially reversed the suppressive effect of miR-185-5p in TPC cells.

Conclusion: Our findings suggest FOXD2-AS1 functions as an oncogene and promotes the tumor progression and metastasis in PTC, which might serve as a promising prognostic biomarker and potential therapeutic target for PTC patients.