TMEM176B inhibits ovarian cancer progression by regulating EMT via the Wnt/β-catenin signaling pathway.

Publisher: BioMed Central Country of Publication: England NLM ID: 101190741 Publication Model: Electronic Cited Medium: Internet ISSN: 1479-5876 (Electronic) Linking ISSN: 14795876 NLM ISO Abbreviation: J Transl Med Subsets: MEDLINE

Original Publication: [London] : BioMed Central, 2003-

Epithelial-Mesenchymal Transition*/genetics ; Wnt Signaling Pathway*/genetics ; Disease Progression* ; Ovarian Neoplasms*/pathology ; Ovarian Neoplasms*/genetics ; Ovarian Neoplasms*/metabolism ; Membrane Proteins*/metabolism ; Membrane Proteins*/genetics ; Mice, Nude* ; Cell Proliferation*/genetics ; Gene Expression Regulation, Neoplastic*; Humans ; Female ; Animals ; Cell Line, Tumor ; Neoplasm Metastasis ; Prognosis ; Cell Movement/genetics ; Middle Aged ; Mice ; Carcinogenesis/genetics ; Carcinogenesis/pathology ; Mice, Inbred BALB C ; Cell Adhesion/genetics ; beta Catenin/metabolism ; Kaplan-Meier Estimate

Competing Interests: Declarations. Ethics approval and consent to participate: This study was performed in line with the principles of the Declaration of Helsinki. Animal experiment was conducted according to the Institutional Animal Care and Use Committee of the Model Animal Research Center. The criteria for tissue included an original histological diagnosis of OC, and the efficiency of clinical pathological data. Each patient provided informed consent. Approval was granted by the Ethics. Consent for publication: All authors have approved the publication of this manuscript. Competing interests: The authors declare no competing interests. Acknowledgements and funding: This work was supported by the Youth Fund of Liaocheng People’s Hopsital (LYQN201908), the “Youth Innovation Team Plan” of Shandong Province Higher Education (2022KJ111), the affiliated hospital (teaching hospital) research and development foundation of Shandong Second Medical University (2024FYQ064 and 2024FYM137), and the Natural Science Foundation of Shandong Province (ZR2022MH304).
Background: Ovarian cancer (OC) is recognized as one of the deadliest forms of gynecological cancer, approximately two-thirds of patients have already developed metastasis when they are diagnosed. The function of transmembrane protein 176B (TMEM176B) in the progression of OC remains elusive. This study aimed to investigate the role and molecular mechanism of TMEM176B on OC proliferation and metastasis.
Method: Expression of TMEM176B in OC and normal tissues were determined from the TCGA, GTEx, and CPTAC databases, and verified by patient-derived tissue samples. We analysed the prognostic relevance of TMEM176B in OC via Kaplan‒Meier (K‒M) survival curves and receiver operating characteristic (ROC) curves. Subsequent in vitro assays, including the CCK8 assay, colony formation assay, wound healing assay, and transwell assay, were performed to detect the influence of TMEM176B on cell proliferation and metastasis. Furthermore, a tumorigenesis study in nude mice was conducted to confirm the suppressive impact of TMEM176B on OC. RNA sequencing (RNA-seq) was utilized to uncover the mechanisms of TMEM176B on OC progression. Spearman correlation analysis was used to calculate the correlations between TMEM176B and cell adhesion, DNA replication, and the Wnt/β-catenin pathway. Finally, the role of TMEM176B in regulating the epithelial-mesenchymal transition (EMT) depending on the Wnt/β-catenin pathway was evaluated using LiCl agonist.
Result: The mRNA expression of TMEM176B was significantly downregulated in OC tissues, with lower TMEM176B correlating with a worse prognosis. Moreover, higher tumor stage and tumor grade were associated with a lower TMEM176B protein level. Consistent with these findings, OC tissues exhibited significantly reduced of TMEM176B compared to normal ovarian tissue from patients. In vitro studies indicated that TMEM176B knockdown increased both the proliferation, metastasis and EMT levels of OC cells, while TMEM176B overexpression had the opposite effects. In vivo investigations reinforced that TMEM176B significantly inhibited the progression of OC. RNA-seq analysis demonstrated that TMEM176B enhanced cell adhesion, diminished DNA replication, and suppressed EMT through the regulation of the Wnt/β-catenin signaling pathway, effectively obstructing the proliferation and metastasis of OC cells and impeding the disease's progression.
Conclusions: TMEM176B inhibited EMT in OC cells by controlling the activation of the Wnt/β-catenin pathway. This mechanism underscored the diagnostic and prognostic potential of TMEM176B for OC and highlights its tumor-suppressive properties as a promising therapeutic candidate.
(© 2025. The Author(s).)

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LYQN201908 Youth Fund of Liaocheng People's Hopsital; 2022KJ111 "Youth Innovation Team Plan" of Shandong Province Higher Education; 2024FYQ064 affiliated hospital (teaching hospital) research and development foundation of Shandong Second Medical University; 2024FYM137 affiliated hospital (teaching hospital) research and development foundation of Shandong Second Medical University; ZR2022MH304 Natural Science Foundation of Shandong Province

Keywords: Epithelial-to-mesenchymal transition; Ovarian cancer; TMEM176B; Wnt/β-catenin signaling pathway

0 (Membrane Proteins)
0 (beta Catenin)

Date Created: 20250320 Date Completed: 20250320 Latest Revision: 20250322

20250324

PMC11921618

10.1186/s12967-025-06362-0

40108613