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 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 through CCK-8, EdU staining, colony formation and cell invasion assays and 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 and suppress tumor growth of PTC . 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.