HIF-1α Regulates the Progression of Cervical Cancer by Targeting YAP/TAZ

Abstract

Cervical carcinoma is one of the serious pernicious cancers that influence women’s health. Invasion and metastasis are the chief reason of poor prognosis of cervical carcinoma. Hypoxia-inducible factor-1α (HIF-1α) is a significant regulatory factor of intracellular oxygen supersession, and its expression or increased activity is closely related to the arise and expansion of various human tumors. However, the relationship between HIF-1α (hypoxia-inducible factor 1) and Hippo pathway target gene Yes-related protein (YAP) and transcriptional coactivator (TAZ) in cervical carcinoma remains unclear. Here, we studied the clinical correlation of HIF-1α and YAP/TAZ expression in normal tissues, cervical intraepithelial neoplasia (CIN), and cervical squamous cell carcinoma (CSCC). In order to analyze the role of HIF-1α in CCSC in vitro, SiHa cells with high expression of HIF-1α and C33a cells with low expression of HIF-1α were screened by detection. After transfection with lentivirus, HIF-1α levels were downregulated in SiHa cells and upregulated in C33a Cells, respectively. Then, the expression of HIF-1α in transfected cervical cancer cells Siha and C33a was detected by qRT-PCR and Western blot, and the expression of YAP/TAZ was detected in cervical squamous cell carcinoma cells after HIF-1α expression was altered. To explore HIF-1α role in cell proliferation, invasion, and metastasis, we examined the changes of cell function in cervical cancer cells with HIF-1α overexpression and inhibition by MTT assay, wound healing assay, Transwell test, and other cell function tests. At the same time, HIF-1α overexpression and HIF-1α inhibition cervical cancer cells were transplanted into nude mice, and tumors were isolated from the nude mice, and tumor volume and weight were observed. In conclusion, HIF-1α significantly promotes the proliferation, invasion, and migration of cervical carcinoma cells by upregulating YAP/TAZ. In addition, YAP/TAZ, the target gene of Hippo pathway, plays an important role in CCSC cells, pointing out that HIF-1α is provided with treatment potential for the treatment of CCSC.