PDHB-AS suppresses cervical cancer progression and cisplatin resistance via inhibition on Wnt/β-catenin pathway
Chi Chi, Wenjie Hou, Yi Zhang, Jie Chen, Zongji Shen, Youguo Chen, Min Li
Abstract
Cervical cancer (CC) is the most prevalent gynecological malignancy occurring in the cervix. Long non-coding RNAs (lncRNAs) can act as oncogenes or anti-oncogenes in CC development. Here, we investigated the functional role and detailed mechanism of lncRNA pyruvate dehydrogenase E1 subunit beta antisense (PDHB-AS) in CC. At first, we found that PDHB-AS was significantly down-regulated in CC cells. Besides, overexpression of PDHB-AS repressed CC cell malignant behaviors. HKF-derived exosomes carried miR-4536-5p to CC cells and thereby inhibited PDHB-AS expression. Moreover, PDHB-AS inactivated the Wnt/β-catenin pathway via impeding the nuclear translocation of β-catenin in CC cells. In addition, miR-582-5p could bind with both PDHB-AS and Dickkopf-1 (DKK1). PDHB-AS recruited poly(A) binding protein cytoplasmic 1 (PABPC1) to inhibit Wnt7b expression. PDHB-AS interacted with RNA-binding motif protein X-linked (RBMX) to regulate cisplatin resistance in CC. Finally, we conducted in vivo experiments to confirm that HKF promoted CC tumor growth whereas PDHB-AS suppressed CC tumor growth. Collectively, PDHB-AS plays a tumor-suppressive role in the progression of CC, which suggests the therapeutic potential of PDHB-AS for CC.