Mechanism study of FEM1C promoting breast cancer progression via the ELAVL1/OPA1 axis-mediated mitochondrial fusion
10.12354/j.issn.1000-8179.2025.20250245
- VernacularTitle:Fem-1同系物C通过调节ELAVL1/OPA1轴介导的线粒体融合促进乳腺癌进展的机制研究
- Author:
Fan YAN
1
;
Li SU
1
;
Tian TIAN
1
;
Yang MENGMENG
1
;
Zhang LULU
1
;
Zhao SUZHEN
1
Author Information
1. 河南省中医院(河南中医药大学第二附属医院)甲状腺乳腺病科(郑州市 450000)
- Publication Type:Journal Article
- Keywords:
breast cancer;
Fem-1 homolog C(FEM1C);
ELAVL1;
OPA1;
mitochondrial fusion
- From:
Chinese Journal of Clinical Oncology
2025;52(10):487-493
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the role of Fem-1 homolog C(FEM1C)in breast cancer progression and elucidate its underlying regulat-ory mechanism.Methods:The expression of FEM1C in breast cancer tissues and cells were detected with qPCR.The binding of FEM1C to ELAVL1 protein was predicted with an online database and validated by CoIP analysis;and the binding of ELAVL1 protein to OPA1 mRNA was predicted by using the starBase database and validated by RIP analysis.Next,breast cancer cell MDA-MB-231 was transfected with FEM1C shRNA(sh-FEM1C)or overexpression vector(FEM1C)or/and ELAVL1 overexpression vector(ELAVL1)or/and OPA1 overexpression vector(OPA1),or treated with 100 μM Mdivi-1,an DRP1 inhibitor,or MYLS22,an OPA1 inhibitor.Finally,nude mice were injected with sh-FEM1C lentiviral vectors to construct xenograft tumor models,and tumor growth was monitored.Results:The expression of FEM1C was upregu-lated in breast cancer tissues(P<0.01).Silencing FEM1C inhibited the proliferation,induced apoptosis,promoted the expression of auto-phagy protein LC3 Ⅱ/Ⅰ,inhibited p62 protein expression,upregulated the protein level of PINK1 in mitochondrial,promoted the expres-sion of mitochondrial fission proteins DRP1 and MIEF2,and inhibited the expression of fusion proteins OPA1 and MFN1 in MDA-MB-231 cells(P<0.01).Mdivi-1 treatment inhibited DRP1 expression(P<0.01),but had no effect on cell viability(P>0.05);MYLS22 treatment inhibited OPA1 expression and counteracted the effect of FEM1C overexpression on MDA-MB-231 cells(P<0.01).Mechanistic studies revealed that FEM1C binds to ELAVL1 protein and promotes its expression(P<0.01);ELAVL1 protein stabilizes OPA1 mRNA by binding to it and upregu-lates OPA1 protein levels(P<0.01).Overexpression of OPA1 reversed the effect of FEM1C silencing on MDA-MB-231 cells(P<0.01).In vivo results showed that knockdown of FEM1C inhibited tumor growth in vivo(P<0.01).Conclusions:FEM1C promotes the stability of OPA1 mRNA by upregulation of ELAVL1 protein to promote mitochondrial fusion and inhibit autophagy,thereby promoting breast cancer progression.
