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LncRNA HOXA-AS2 facilitates tumorigenesis and progression of papillary thyroid cancer through modulating miR-15a-5p/HOXA3 axis.

Human Gene Therapy 2018 October 31
Long non-coding RNA HOXA-AS2 has been found to be an oncogene in several types of human malignant tumors. However, the role HOXA-AS2 in regulating the occurrence and development of papillary thyroid cancer (PTC) is still unclear. This study focused on investigating the function and mechanism of HOXA-AS2 in PTC progression. Using qRT-PCR analysis, we found that HOXA-AS2 was differentially expressed in PTC tissues and cell lines. The result of Kaplan Meier analysis indicated that the overall survival rate of patients with higher level of HOXA-AS2 was lower than those with relative lower level of HOXA-AS2. Loss-of-functional assays revealed that HOXA-AS2 knockdown inhibited PTC progression by inhibiting cell proliferation, migration and invasion and accelerating cell apoptosis. Mechanistically, HOXA3 was found to be a nearby gene of HOXA-AS2. Loss-of-function assays showed the same function of HOXA3 knockdown with HOXA-AS2 knockdown. According to the result of subcellular fractionation assay, the expression of HOXA-AS2 was abundant in the cytoplasm of PTC cells. Further mechanism investigation revealed that FOXD2-AS1 upregulated the expression of HOXA3 by sponging miR-15a-5p. Rescue assays demonstrated that the function of HOXA-AS2-miR-15a-5p-HOXA3 axis in PTC progression.

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