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

Abstract

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.

Long non-coding RNA HOXA-AS2 may serve as a new therapeutic target and promising prognostic market for most of cancers

“…In the end, 12 articles with a total of 796 patients (Table 1) were included in this study. There were 8 types of cancer in these 12 literatures, including 2 cases of lung cancer [17,18], 2 of thyroid cancer [19,20], 1 of bladder cancer [21], 1 of breast cancer [22], 1 of gastric cancer [23], 2 of colorectal cancer [9,10], 1 of osteosarcoma [24] and 2 cases of liver cancer [14,25]. All the 12 articles come from China (Table 1).…”

“…Through the lnCAR database, we found that HOXA-AS2 can regulate the expression of mRNA through miR-372-3p, miR-373-3p, miR-302a-3p, miR-519d-3p, miR-106b-5p, miR-520b, miR-302e, miR-520e, miR-106a-5p, miR-302d-3p, miR-302c-3p, MiR-302b-3p, miR-20a-5p, miR-520d-3p, miR-17-5p, miR-93-5p, miR-20b-5p, miR-520c-3p and miR-520a-3p, and further participate in the occurrence and development of tumor. At present, studies have confirmed that long-chain non-coding RNAHOXA-AS2 can take part in the progression of AML, thyroid papillary carcinoma, HCC and breast cancer throuh target regulating of miR-520c-3p [12,14,19,22]. In addition, HOXA-AS2 can promote the malignant progression of non-small cell lung cancer, thyroid papillary carcinoma and liver cancer through miRNA-216a-5p, miR-520a-3p, miR-15a-5p and miR-125b [17,18,20,21].…”

Long non‑coding RNA BRM promotes proliferation and invasion of papillary thyroid carcinoma by regulating the microRNA‑331‑3p/SLC25A1 axis

“…Moreover, several studies revealed the roles of lncRNAs in the regulation of PTC progression. For example, Xia et al (33) reported that lncRNA HOXA-AS2 was upregulated in PTC tissues and promoted migration and invasion of PTC cells by regulating the miR-520c-3p/S100A4 pathway. Wang et al (34) demonstrated that LINC01186 suppressed proliferation and invasion of PTC cells by decreasing the expression of YAP1 and increasing LATS1 expression.…”

NNT‐AS1 enhances bladder cancer cell growth by targeting miR‐1301‐3p/PODXL axis and activating Wnt pathway

“…[31][32][33] Mechanistically, lncRNAs could act as miRNA spongers to modulate miRNA downstream mRNA via ceRNA network. 34,35 miR-1301-3p has been reported to inhibit cell proliferation, induce cell apoptosis, and regulate cell-cycle progression via directly targeting ICT1 in breast cancer. 36 miRNA-1301 directly targets to N-Ras and inhibits glioma cell proliferation.…”