期刊
CANCER CELL INTERNATIONAL
卷 21, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s12935-021-01937-5
关键词
miR-190; TET1; CDKN1B; Methylation; Bladder epithelial cell transformation
类别
资金
- Natural Science Foundation of China [NSFC81601849]
- Zhejiang Provincial Medicine and Health Technology Project [2019RC217]
- Wenzhou Science and Technology Bureau [Y20180109]
In this study, miR-190 was found to play an important role in the development of bladder cancer (BC) by downregulating CDKN1B and promoting the malignant transformation of bladder epithelial cells. These findings suggest that miR-190 may enhance BC cell transformation by inhibiting CDKN1B, providing a deeper understanding of its regulatory role in BC.
Background Although miR-190 has been reported to be related to human diseases, especially in the development and progression of cancer, its expression in human bladder cancer (BC) and potential contribution to BC remain unexplored. Methods RT-qPCR was used to verify the expression level of miR-190 and CDKN1B. Flow cytometry (FCM) assays were performed to detect cell cycle. Soft agar assay was used to measure anchorage-independent growth ability. Methylation-Specific PCR, Dual-luciferase reporter assay and Western blotting were used to elucidate the potential mechanisms involved. Results Our studies revealed that downregulation of the p27 (encoded by CDKN1B gene) protein is an important event related to miR-190, promoting the malignant transformation of bladder epithelial cells. miR-190 binds directly to CDKN1B 3'-UTR and destabilizes CDKN1B mRNA. Moreover, miR-190 downregulates TET1 by binding to the TET1 CDS region, which mediates hypermethylation of the CDKN1B promoter, thereby resulting in the downregulation of CDKN1B mRNA. These two aspects led to miR-190 inhibition of p27 protein expression in human BC cells. A more in-depth mechanistic study showed that c-Jun promotes the transcription of Talin2, the host gene of miR-190, thus upregulating the expression of miR-190 in human BC cells. Conclusions In this study, we found that miR-190 plays an important role in the development of BC. Taken together, these findings indicate that miR-190 may promote the malignant transformation of human urothelial cells by downregulating CDKN1B, which strengthens our understanding of miR-190 in regulating BC cell transformation.
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