2. Academic Validation
  3. CHN1 promotes epithelial-mesenchymal transition via the Akt/GSK-3β/Snail pathway in cervical carcinoma

CHN1 promotes epithelial-mesenchymal transition via the Akt/GSK-3β/Snail pathway in cervical carcinoma

  • J Transl Med. 2021 Jul 8;19(1):295. doi: 10.1186/s12967-021-02963-7.
Haoqi Zhao 1 2 3,  Lan Wang 4,  Shufang Wang 1 2 5,  Xihua Chen 2,  Min Liang 1 2,  Xin Zhang 1 2,  Jiedong Wang 1 2,  Xiangbo Xu 6
Affiliations

Affiliations

  • 1 Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China.
  • 2 Reproductive Physiology Laboratory, National Research Institute for Family Planning, Beijing, 100081, China.
  • 3 National Engineering and Research Center of Continuous Casting Technology, China Iron and Steel Research Institute Group, Beijing, 100081, China.
  • 4 Biopharmaceutical R&D Center, Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou, 215126, Jiangsu, China.
  • 5 Department of Forensic Medicine, Xinxiang Medical University, Xinxiang, 453003, Henan, China.
  • 6 Reproductive Physiology Laboratory, National Research Institute for Family Planning, Beijing, 100081, China. [email protected].
PMID: 34238315 DOI: 10.1186/s12967-021-02963-7
Abstract

Background: Metastasis and invasion are crucial in determining the mortality of cervical carcinoma (CC) patients. The epithelial-mesenchymal transition (EMT) is now a universal explanation for the mechanisms of tumor metastasis. Α-chimeric protein (α-chimaerin, CHN1) plays an important role in the regulation of signal transduction and development. However, the molecular regulatory relationships between CHN1 and CC progression in relation to EMT have not yet been identified.

Methods: The expression of CHN1 in CC tissues, adjacent tissues, and lymph node metastases from CC patients was detected by immunohistochemistry. Upregulation and knockdown of CHN1 were achieved by transfection of CC cells. The effect of CHN1 on cell proliferation was determined by CCK-8 and plate clone formation assays. Changes in migration and invasion capabilities were evaluated using scratch migration and transwell invasion assays. The effect of CHN1 overexpression and interference on xenograft tumor growth was determined by tumor weight and pathological analyses. The expression of EMT-related mRNAs was measured by qRT-PCR in transfected CC cells. EMT-related proteins and Akt/GSK-3β/Snail signaling pathway-related proteins were also evaluated by western blotting.

Results: CHN1 was overexpressed in CC tissues and was associated with lymph node metastasis and low survival in CC patients. Overexpression of CHN1 promoted cell proliferation, migration, and invasion in CC cells. In contrast, silencing of CHN1 inhibited these phenomena. Overexpression of CHN1 promoted tumor formation in an in vivo xenograft tumor mouse model, with increased tumor volumes and weights. In addition, CHN1 induced the expression of EMT-related transcription factors, accompanied by the decreased expression of epithelial markers and increased expression of mesenchymal markers. The Akt/GSK-3β/Snail signaling pathway was activated by overexpression of CHN1 in vitro, and activation of this pathway was inhibited by the signaling pathway inhibitor LY294002.

Conclusion: These results suggest that CHN1 promotes the development and progression of cervical carcinoma via the Akt/GSK-3β/Snail pathway by inducing EMT.

Keywords

Akt/GSK-3β/Snail signaling pathway; CHN1; Cervical carcinoma; Epithelial-mesenchymal transition (EMT).

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