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TFAP2A knockdown reduced proliferation and migration, promoted apoptosis, and bound the PD‑L1 promoter; PD‑L1 rescued TFAP2A expression, while in vivo assays showed enhanced tumor growth, defining a TFAP2A/PD‑L1 positive feedback loop with clinical 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is TFAP2A’s role in cervical cancer according to the study?","Question",{"text":63,"@type":64},"TFAP2A is overexpressed in cervical cancer and is associated with worse clinical outcomes, including higher tumor stage, lymph node metastasis, and poor survival.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How does TFAP2A affect cervical cancer cell behavior experimentally?",{"text":68,"@type":64},"TFAP2A knockdown inhibits proliferation and migration of cervical cancer cells and promotes apoptosis.",{"name":70,"@type":61,"acceptedAnswer":71},"What relationship between TFAP2A and PD‑L1 was identified?",{"text":72,"@type":64},"TFAP2A binds the PD‑L1 promoter, and PD‑L1 can rescue TFAP2A expression, establishing a positive feedback loop between TFAP2A and 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\nJUNYUAN YANG , YANG GAO , SINJIE YAO, SHIMENG WAN and HONGBING CAI  \nDepartment of Gynecological Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China  \nReceived December 2, 2022; Accepted April 10, 2023  \nDOI: 10. 3892/or.2023.8551  \nAbstract. Transcription factor AP‑2 alpha (TFAP2A) is a critical cell growth regulator that is overexpressed in various tumor tissues. However, its role in the development of cervical cancer remains unknown. In the present study, public data‑ bases were thus explored and a higher expression of TFAP2A was found in cervical cancer. A total of 131 clinical samples were collected and it was also identified that TFAP2A was highly expressed in cervical tumor tissues. TFAP2A was also found to be associated with a higher tumor stage, lymph node metastasis and a poor patient survival. In vitro experiments revealed that the knockdown of TFAP2A inhibited the prolif‑ eration and migration of cervical cancer cells and promoted apoptosis. Furthermore, it was observed that TFAP2A could bind the programmed death‑ligand 1 (PD‑L1) promoter region and PD‑L1 rescued TFAP2A expression . In vivo experi‑ ments also revealed that TFAP2A promoted tumor growth. Collectively, in the present study it was demonstrated that TFAP2A is a transcription factor of PD‑L1 and a prognostic factor with clinical value, identifying a positive feedback loop ofTFAP2A/PD‑L1.  \nIntroduction  \nCervical cancer is a very lethal type of cancer with a high incidence and mortality (1), ~80% of them are cervical squa‑ mous cell carcinoma (2) . Although in recent years, with the ongoing developments of treatment technologies and the broad availability of the HPV vaccine the incidence and mortality rate of cervical cancer have decreased (3), the therapeutic effi‑ cacy remains limited, and the main cause of the mortality of cervical cancer patients is the invasive metastasis of the tumor.  \nCorrespondence to: Dr Hongbing Cai, Department of Gynecological Oncology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuchang, Wuhan, Hubei 430071, P.R. China  \nE‑mail: [chb2105@163.com](chb2105@163.com)  \n*Contributed equally  \nKey words: transcription factor AP‑2 alpha, cervical cancer, programmed death‑ligand 1, proliferation, migration  \nTherefore, the mining of molecular markers that can effec‑ tively modulate the invasive metastasis of cervical cancer maybe beneficial in order to reduce the mortality rate of patients with cervical cancer.  \nTFAP2A is a crucial mediator of embryonic development that is aberrantly overexpressed in various types of cancer, including basal‑squamous bladder cancer (4), pancreatic cancer (5), gastric cancer (6), lung adenocarcinoma (7), naso‑ pharyngeal carcinoma (8) and ovarian cancer (9); TFAP2A mainly functions as a transcription factor that can promote the expression of particular genes, including direct upregu‑ lation of bone morphogenetic protein 4 (BMP4) promoting angiogenesis and leads to drug resistance (10) and induction of keratin 16 and transforming growth factor‑β (TGF‑β) overexpression promoting the epithelial‑mesenchymal transition of tumors (11,12) . Accumulating evidence has demonstrated that TFAP2A has potential use as a diagnostic marker for specific tumors, and it is involved in cancer cell proliferation, invasion and migration (13) . A high TFAP2A expression has been shown to be associated with a poor tumor prognosis and an increased risk of recurrence (14) . It is also involved in tumor adaptability to hypoxia and food deprivation (8,15) . The aforementioned findings suggested that TFAP2A is involved in cancer genesis and progression. However, the role of TFAP2A in cervical cancer remains unknown.  \nProgrammed death‑ligand 1 (PD‑L1) is mainly expressed on the surface of tumor cells, and an increased PD‑L1 expres‑ sion is associated with the poor survival of","cbCaihtXEIhXds6g","https://ap.wps.com/l/cbCaihtXEIhXds6g","pdf",13574671,14,"English","# Abstract\n# Introduction\n# Materials and methods","[{\"question\":\"What is TFAP2A’s role in cervical cancer according to the study?\",\"answer\":\"TFAP2A is overexpressed in cervical cancer and is associated with worse clinical outcomes, including higher tumor stage, lymph node metastasis, and poor survival.\"},{\"question\":\"How does TFAP2A affect cervical cancer cell behavior experimentally?\",\"answer\":\"TFAP2A knockdown inhibits proliferation and migration of cervical cancer cells and promotes apoptosis.\"},{\"question\":\"What relationship between TFAP2A and PD‑L1 was identified?\",\"answer\":\"TFAP2A binds the PD‑L1 promoter, and PD‑L1 can rescue TFAP2A expression, establishing a positive feedback loop between TFAP2A and PD‑L1.\"}]","TFAP2A promotes cervical cancer via a positive feedback pathway with PD‑L1 | PDF",1790227366,35]