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

Azierguli Abudoukerimu; Axiangu Hasimu; Abudouhabaer Abudoukerimu; Gulijiannaiti Tuerxuntuoheti; Yixin Huang; Jie Wei; Tao Yu; Hong Ma; Delixiati Yimiti

doi:10.1155/2022/3814809

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

J Oncol. 2022 May 25:2022:3814809. doi: 10.1155/2022/3814809. eCollection 2022.

Authors

Azierguli Abudoukerimu^{1

2

3}, Axiangu Hasimu⁴, Abudouhabaer Abudoukerimu⁵, Gulijiannaiti Tuerxuntuoheti⁶, Yixin Huang², Jie Wei⁷, Tao Yu⁸, Hong Ma^{3

4}, Delixiati Yimiti^{1

2}

Affiliations

¹ Department of Occupational and Environmental Health, School of Public Health, Xinjiang Medical University, Urumqi, 830017, China.
² Department of Microbiology, School of Basic Medical Science, Xinjiang Medical University, Urumqi, 830017, China.
³ Xinjiang Key Laboratory of Molecular Biology for Endemic Disease, Urumqi, 830017, China.
⁴ Department of Pathology, School of Basic Medical Science, Xinjiang Medical University, Urumqi, 830017, China.
⁵ Department of Science, Hotan Normal College, Hotan 848000, Xinjiang Uygur Autonomous Regions, China.
⁶ Department of Linguistic, Hotan Normal College, Hotan 848000, Xinjiang Uygur Autonomous Regions, China.
⁷ Institute of Veterinary Medicine, Xinjiang Academy of Animal Science, Urumqi 830000, Xinjiang Uygur Autonomous Regions, China.
⁸ Shandong Institute of Parasitic Diseases, Shandong First Medical University & Shandong Academy of Medical, Jinan 272033, Shandong Province, China.

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.