Roles of lncRNA UCA1-miR-18a-SOX6 axis in preventing hypoxia injury following cerebral ischemia.

The present study aimed to elucidate the roles and possible molecular mechanisms of long noncoding RNA (lncRNA) urothelial carcinoma associated 1 (UCA1) in neuronal pheochromocytoma (PC)-12 cells under hypoxic conditions. The neuronal PC-12 cells were exposed to hypoxic and normoxic conditions followed by the measurement of the expression of lncRNA UCA1. In addition, the cells were transfected with short hairpin RNAs (sh-RNAs) against UCA1 (sh-UCA1), SOX6 (sh-SOX6), negative control (sh-NC), pEX-SOX6, pEX, miR-18a mimic, mimic NC, miR-18a inhibitor, and inhibitor NC. Under different treatments of transfection, cell viability and migration and invasion potential were analyzed. In addition, the induction of apoptosis was investigated by studying the expression profiles of apoptosis-related proteins. Hypoxia treatment significantly enhanced the expression of UCA1, which in turn induced injury in PC-12 cells characterized by the inhibition of cell viability, the reduction in migration and invasion potential, and the promotion of cell apoptosis. Moreover, the suppression of UCA1 alleviated the hypoxia injury. In addition, the relationship between UCA1 and miR-18a and between miR-18a and SRY-box containing gene 6 (SOX6) were explored. MiR-18a was found to be a direct target of UCA1, an upregulation of which mediated the effects of suppression of UCA1 (alleviated hypoxic injury). Besides, SOX6 was found to be a target of miR-18a whose expression could be negatively regulated by miR-18a. An overexpression of SOX6 could also aggravate hypoxia injury in PC-12 cells, whereas a knockdown of SOX6 exhibited contrary results. Our findings indicated that the down-regulation of UCA1 promoted the expression of miR-18a that led to a reduction in the expression of its target protein, SOX6, thereby contributing to the hypoxia injury following cerebral ischemia.