Mitofusin-2 enhances cervical cancer progression through Wnt/β-catenin signaling
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Overexpression of mitofusin-2 (MFN2), a mitochondrial fusionprotein, is frequently associated with poor prognosis in cervicalcancer patients. Here, I aimed to investigate the involvementof MFN2 in cervical cancer progression and determine theeffect of MFN2 on prognosis in cervical cancer patients. Aftergenerating MFN2-knockdown SiHa cells derived from squamouscell carcinoma, I investigated the effect of MFN2 on SiHa cellproliferation using the Cell Counting Kit-8 assay and determinedthe mRNA levels of proliferation markers. Colony-formingability and tumorigenesis were evaluated using a colonyformationassay and tumor xenograft mouse models. The migratoryand invasive abilities associated with MFN2 were measuredusing wound-healing and invasion assays. Wnt/β-cateninmediatedepithelial-mesenchymal transition (EMT) markers relatedto MFN2 were assessed through quantitative RT-PCR. MFN2-knockdown SiHa cells exhibited reduced proliferation,colony formation, migration, invasion, and tumor formation invivo. The motility of SiHa cells with MFN2 knockdown wasreduced through Wnt/β-catenin-mediated EMT inhibition. MFN2promoted cancer progression and tumorigenesis in SiHa cells. Overall, MFN2 could serve as a therapeutic target and a novelbiomarker for cervical cancer.
Abstract
Overexpression of mitofusin-2 (MFN2), a mitochondrial fusionprotein, is frequently associated with poor prognosis in cervicalcancer patients. Here, I aimed to investigate the involvementof MFN2 in cervical cancer progression and determine theeffect of MFN2 on prognosis in cervical cancer patients. Aftergenerating MFN2-knockdown SiHa cells derived from squamouscell carcinoma, I investigated the effect of MFN2 on SiHa cellproliferation using the Cell Counting Kit-8 assay and determinedthe mRNA levels of proliferation markers. Colony-formingability and tumorigenesis were evaluated using a colonyformationassay and tumor xenograft mouse models. The migratoryand invasive abilities associated with MFN2 were measuredusing wound-healing and invasion assays. Wnt/β-cateninmediatedepithelial-mesenchymal transition (EMT) markers relatedto MFN2 were assessed through quantitative RT-PCR. MFN2-knockdown SiHa cells exhibited reduced proliferation,colony formation, migration, invasion, and tumor formation invivo. The motility of SiHa cells with MFN2 knockdown wasreduced through Wnt/β-catenin-mediated EMT inhibition. MFN2promoted cancer progression and tumorigenesis in SiHa cells. Overall, MFN2 could serve as a therapeutic target and a novelbiomarker for cervical cancer.
참고문헌 (30)
- Dasari S, "Cervical cancer : biomarkers for diagnosis and treatment", Clin Chim Acta, 445, pp.7~11 (2015)
- Senapathy JG, "The present scenario of cervical cancer control and HPV epidemiology in India : an outline", Asian Pac J Cancer Prev, 12, pp.1107~1115 (2011)
- Cohen PA, "Cervical cancer", Lancet, 393, pp.169~182 (2019)
- Targonski CA, "Uncovering biomarker genes with enriched classification potential from Hallmark gene sets", Sci Rep, 9, pp.9747~ (2019)
- Zong WX, "Mitochondria and Cancer", Mol Cell, 61, pp.667~676 (2016)
- Vyas S, "Mitochondria and cancer", Cell, 166, pp.555~566 (2016)
- Youle RJ, "Mitochondrial fission, fusion, and stress", Science, 337, pp.1062~1065 (2012)
- Hoppins S, "The machines that divide and fuse mitochondria", Annu Rev Biochem, 76, pp.751~780 (2007)
- Ehses S, "Regulation of OPA1 processing and mitochondrial fusion by m-AAA protease isoenzymes and OMA1", J Cell Biol, 187, pp.1023~1036 (2009)
- Kowald A, "The evolution and role of mitochondrial fusion and fission in aging and disease", Commun Integr Biol, 4, pp.627~629 (2011)
- Senft D, "Regulators of mitochondrial dynamics in cancer", Curr Opin Cell Biol, 39, pp.43~52 (2016)
- Karimi D, "FIS1 overexpression is correlated with tumor metastasis in gastric adenocarcinoma", J Gastrointest Cancer, 53, pp.466~471 (2022)
- Liu X, "Mfn2 inhibits proliferation and cell-cycle in Hela cells via Ras-NF-kappaB signal pathway", Cancer Cell Int, 19, pp.197~ (2019)
- Xu K, "MFN2 suppresses cancer progression through inhibition of mTORC2", Akt signaling, 2017, pp.7, 41718~
- Jin B, "Anti-tumour efficacy of mitofusin-2 in urinary bladder carcinoma", Med Oncol, 1, pp.S373~380 (2011)
- Fang CL, "Overexpression of mitochondrial GTPase MFN2 represents a negative prog-nostic marker in human gastric cancer and its inhibition exerts anti-cancer effects", J Cancer, 8, pp.1153~1161 (2017)
- Lou Y, "Mitofusin-2 over-expresses and leads to dysregulation of cell cycle and cell invasion in lung adenocarcinoma", Med Oncol, 32, pp.132~ (2015)
- Ahn SY, "Mitofusin-2expression is implicated in cervical cancer pathogenesis", Anticancer Res, 38, pp.3419~3426 (2018)
- Thiery JP, "Epithelial-mesenchymal transitions in development and disease", Cell, 139, pp.871~890 (2009)
- Guan X, "E-cadherin can replace N-cadherin during secretory-stage enamel development", PLoS One, 9, pp.e102153~ (2014)
- van Roy F, "The cell-cell adhesion molecule E-cadherin", Cell Mol Life Sci, 65, pp.3756~3788 (2008)
- Taciak B, "Wnt signaling pathway in development and cancer", J Physiol Pharmacol, 69(2), pp.185~196 (2018)
- Purohit PK, "MiR-195 regulates mitochondrial function by targeting mitofusin-2 in breast cancer cells", RNA Biol, 16, pp.918~929 (2019)
- Yan H, "Yap regulates gastric cancer survival and migration via SIRT1", Mfn2, Oncol Rep, pp.2018, 39[DOI]
- Sun Q, "Mfn2 inhibits chronic rejection of the rat abdominal aorta by regulating TGFbeta1levels", Transpl Immunol, 55, pp.101211~ (2019)
- Wang W, "Mitofusin-2 is a novel direct target of p53", Biochem Biophys Res Commun, 400, pp.587~592 (2010)
- Reya T, "Wnt signalling in stem cells and cancer", Nature, 434, pp.843~850 (2005)
- Yook JI, "A Wnt-Axin2-GSK3beta cascade regulates Snail1 activity in breast cancer cells", Nat Cell Biol, 8, pp.1398~1406 (2006)
- Taketo MM, "Shutting down Wnt signal-activated cancer", Nat Genet, 36, pp.320~322 (2004)
- Cadigan KM, "Wnt signaling : complexity at the surface", J Cell Sci, 119, pp.395~402 (2006)