HIF-1 alpha Regulates the Progression of Cervical Cancer by Targeting YAP/TAZ
JOURNAL OF ONCOLOGY(2022)
摘要
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-1 alpha (HIF-1 alpha) 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-1 alpha (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-1 alpha 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-1 alpha in CCSC in vitro, SiHa cells with high expression of HIF-1 alpha and C33a cells with low expression of HIF-1 alpha were screened by detection. After transfection with lentivirus, HIF-1 alpha levels were downregulated in SiHa cells and upregulated in C33a Cells, respectively. Then, the expression of HIF-1 alpha 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-1 alpha expression was altered. To explore HIF-1 alpha role in cell proliferation, invasion, and metastasis, we examined the changes of cell function in cervical cancer cells with HIF-1 alpha overexpression and inhibition by MTT assay, wound healing assay, Transwell test, and other cell function tests. At the same time, HIF-1 alpha overexpression and HIF-1 alpha 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-1 alpha 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-1 alpha is provided with treatment potential for the treatment of CCSC.
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