2. Academic Validation
  3. ZBTB7A regulates LncRNA HOTAIR-mediated ELAVL1/SOX17 axis to inhibit malignancy and angiogenesis in endometrial carcinoma

ZBTB7A regulates LncRNA HOTAIR-mediated ELAVL1/SOX17 axis to inhibit malignancy and angiogenesis in endometrial carcinoma

  • J Cancer Res Clin Oncol. 2024 Jul 9;150(7):345. doi: 10.1007/s00432-024-05860-w.
Xiao-Hui Zhang 1 2 3 4 5,  Shu-Wei Wu 1 4 5,  Yi-Fan Feng 1 4 5,  Yang-Qin Xie 1 4 5,  Min Li 1 2 3 4,  Ping Hu 6,  Yunxia Cao 7 8 9 10 11
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, 218, Jixi Road, Hefei, Anhui Province, 230022, P. R. China.
  • 2 NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), 218, Jixi Road, Hefei, Anhui Province, 230032, P. R. China.
  • 3 Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, 218, Jixi Road, Hefei, Anhui Province, 230032, P. R. China.
  • 4 Anhui Province Key Laboratory of Reproductive Health and Genetics, 218, Jixi Road, Hefei, Anhui Province, 230032, P. R. China.
  • 5 Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, 218, Jixi Road, Hefei, Anhui Province, 230032, P. R. China.
  • 6 Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, 230022, P. R. China.
  • 7 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, 218, Jixi Road, Hefei, Anhui Province, 230022, P. R. China. caoyunxia6@126.com.
  • 8 NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), 218, Jixi Road, Hefei, Anhui Province, 230032, P. R. China. caoyunxia6@126.com.
  • 9 Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, 218, Jixi Road, Hefei, Anhui Province, 230032, P. R. China. caoyunxia6@126.com.
  • 10 Anhui Province Key Laboratory of Reproductive Health and Genetics, 218, Jixi Road, Hefei, Anhui Province, 230032, P. R. China. caoyunxia6@126.com.
  • 11 Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, 218, Jixi Road, Hefei, Anhui Province, 230032, P. R. China. caoyunxia6@126.com.
PMID: 38981872 DOI: 10.1007/s00432-024-05860-w
Abstract

Background: Endometrial Cancer (EC) is the sixth most frequent Cancer in women worldwide and has higher fatality rates. The pathophysiology of EC is complex, and there are currently no reliable methods for diagnosing and treating the condition. Long non-coding RNA (lncRNA), according to mounting evidence, is vital to the pathophysiology of EC. HOTAIR is regarded as a significant prognostic indicator of EC. ZBTB7A decreased EC proliferation and migration, according to recent studies, however the underlying mechanism still needs to be clarified.

Methods: The research utilized RT-qPCR to measure HOTAIR expression in clinical EC tissues and various EC cell lines. Kaplan-Meier survival analysis was employed to correlate HOTAIR levels with patient prognosis. Additionally, the study examined the interaction between ZBTB7A and HOTAIR using bioinformatics tools and ChIP assays. The experimental approach also involved manipulating the expression levels of HOTAIR and ZBTB7A in EC cell lines and assessing the impact on various cellular processes and gene expression.

Results: The study found significantly higher levels of HOTAIR in EC tissues compared to adjacent normal tissues, with high HOTAIR expression correlating with poorer survival rates and advanced Cancer characteristics. EC cell lines like HEC-1 A and KLE showed higher HOTAIR levels compared to normal cells. Knockdown of HOTAIR in these cell lines reduced proliferation, angiogenesis, and migration. ZBTB7A was found to be inversely correlated with HOTAIR, and its overexpression led to a decrease in HOTAIR levels and a reduction in malignant cell behaviors. The study also uncovered that HOTAIR interacts with ELAVL1 to regulate SOX17, which in turn activates the Wnt/β-catenin pathway, promoting malignant behaviors in EC cells.

Conclusion: HOTAIR is a critical regulator in EC, contributing to tumor growth and poor prognosis. Its interaction with ZBTB7A and regulation of SOX17 via the Wnt/β-catenin pathway underlines its potential as a therapeutic target.

Keywords

Endometrial carcinoma; HOTAIR; SOX17; Wnt-β-catenin pathway; ZBTB7A.

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