Publications
Article type
Year
Sort：
Published
Cited
Download
Issue
Effect of transmembrane protein 196 on migration and invasion of breast cancer
Zhe ZHANG, Jun FAN, Wenbin LIU, Yan XU
Journal of Army Medical University 2022, 44(14): 1455-1465
Published: 30 July 2022
Abstract PDF (2.4 MB) Collect
Downloads：7
Objective

To investigate the effect of transmembrane protein 196 (TMEM196) on the migration and invasion of breast cancer cells.

Methods

The Cancer Genome Atlas (TCGA) and Oncomine database were used to analyze the mRNA expression of TMEM196 in breast cancer. The expression of TMEM196 in breast cancer cells was detected by quantitative real time-polymerase chain reaction (RT-qPCR). Kaplan-Meier database was employed to analyze the effect of TMEM196 on the prognosis of breast cancer patients. The protein level and prognostic effect of TMEM196 were analyzed by tissue microarray. The cohort included 70 paracancerous samples and 160 invasive breast cancer samples from the patients (53.61±13.13 years old) undergoing surgical resection from January 2001 to August 2004, with a follow-up period of 2 to 150 months. Cell proliferation experiment, scratch healing test and Transwell assay were performed to determine the effect of TMEM196 on the proliferation, migration and invasion of breast cancer cells. Western blot assay was used to explore the regulation of TMEM196 on the expression of β-catenin and matrix metalloproteinases 7 (MMP7).

Results

The mRNA and protein levels of TMEM196 were significantly decreased in breast cancer (P<0.05), and notably, this phenomenon was most obvious in triple negative breast cancer (TNBC) cell line MDA-MB-231 and TNBC tissues (P<0.05). Lower expression of TMEM196 was associated with poor overall survival (OS) (HR=0.524, 95%CI: 0.293~0.936, P=0.040). In addition, overexpression of TMEM196 could significantly inhibit the proliferation, migration and invasion of breast cancer cells (P<0.05), while its knockdown can significantly enhances the above abilities (P<0.05). The results of Western blot assay indicated that TMEM196 inhibited the β-catenin/MMP7 signaling pathway and reduced the motility of breast cancer cells (P<0.05). On the contrary, the tumor-promoting effect which caused by knockdown of TMEM196 could be eliminated after adding β-catenin inhibitor (P<0.05).

Conclusion

TMEM196 inhibits the migration and invasion of breast cancer cells by regulating the β-catenin/MMP7 signaling pathway.

Open Access Full Length Article Issue
Zinc finger protein 831 promotes apoptosis and enhances chemosensitivity in breast cancer by acting as a novel transcriptional repressor targeting the STAT3/Bcl2 signaling pathway
Jun Fan, Zhe Zhang, Hongqiang Chen, Dongjiao Chen, Wenbo Yuan, Jingzhi Li, Yong Zeng, Shimeng Zhou, Shu Zhang, Gang Zhang, Jiashen Xiong, Lu Zhou, Jing Xu, Wenbin Liu, Yan Xu
Genes & Diseases 2024, 11(1): 430-448
Published: 29 December 2022
Abstract PDF (6.3 MB) Collect
Downloads：10

Emerging evidence suggested that zinc finger protein 831 (ZNF831) was associated with immune activity and stem cell regulation in breast cancer. Whereas, the roles and molecular mechanisms of ZNF831 in oncogenesis remain unclear. ZNF831 expression was significantly diminished in breast cancer which was associated with promoter CpG methylation but not mutation. Ectopic over-expression of ZNF831 suppressed breast cancer cell proliferation and colony formation and promoted apoptosis in vitro, while knockdown of ZNF831 resulted in an opposite phenotype. Anti-proliferation effect of ZNF831 was verified in vivo. Bioinformatic analysis of public databases and transcriptome sequencing both showed that ZNF831 could enhance apoptosis through transcriptional regulation of the JAK/STAT pathway. ChIP and luciferase report assays demonstrated that ZNF831 could directly bind to one specific region of STAT3 promoter and induce the transcriptional inhibition of STAT3. As a result, the attenuation of STAT3 led to a restraint of the transcription of Bcl2 and thus accelerated the apoptotic progression. Augmentation of STAT3 diminished the apoptosis-promoting effect of ZNF831 in breast cancer cell lines. Furthermore, ZNF831 could ameliorate the anti-proliferation effect of capecitabine and gemcitabine in breast cancer cell lines. Our findings demonstrate for the first time that ZNF831 is a novel transcriptional suppressor through inhibiting the expression of STAT3/Bcl2 and promoting the apoptosis process in breast cancer, suggesting ZNF831 as a novel biomarker and potential therapeutic target for breast cancer patients.

Total 2