Silencing of lncRNA MIR497HG via CRISPR/Cas13d Induces Bladder Cancer Progression Through Promoting the Crosstalk Between Hippo/Yap and TGF-β/Smad Signaling

Abstract

A subset of long non-coding RNAs (lncRNAs), categorized as miRNA-host gene lncRNAs (lnc-miRHGs), is processed to produce miRNAs and involved in cancer progression. This work aimed to investigate the influences and the molecular mechanisms of lnc-miRHGs MIR497HG in bladder cancer (BCa). The miR-497 and miR-195 were derived from MIR497HG. We identified that lnc-miRHG MIR497HG and two harbored miRNAs, miR-497 and miR-195, were downregulated in BCa by analyzing The Cancer Genome Atlas and our dataset. Silencing of MIR497HG by CRISPR/Cas13d in BCa cell line 5637 promoted cell growth, migration, and invasion in vitro. Conversely, overexpression of MIR497HG suppressed cell progression in BCa cell line T24. MiR-497/miR-195 mimics rescued significantly the oncogenic roles of knockdown of MIR497HG by CRISPR/Cas13d in BCa. Mechanistically, miR-497 and miR-195 co-ordinately suppressed multiple key components in Hippo/Yap and transforming growth factor β signaling and particularly attenuated the interaction between Yap and Smad3. In addition, E2F4 was proven to be critical for silencing MIR497HG transcription in BCa cells. In short, we propose for the first time to reveal the function and mechanisms of MIR497HG in BCa. Blocking the pathological process may be a potential strategy for the treatment of BCa.

A Novel Signature for Predicting Prognosis of Smoking-Related Squamous Cell Carcinoma

“…The kelch-like family member 15 (KLHL15) can encode a member of the kelch-like family of proteins and is involved in protein ubiquitination and cytoskeletal organization (Ferretti et al, 2016;Zhou et al, 2019), but few studies focus on cancers. E2F transcription factor 4 (E2F4), a member of the E2F family of transcription factors, plays an important role in inhibiting proliferation-associated genes, and its gene mutation and increased expression are related to different cancers (Gong et al, 2020;Zhuang et al, 2020). In the future, these genes should be deeply investigated roles in SCC.…”

Biological functions and clinical significance of long noncoding RNAs in bladder cancer

“…E2F4 is reported to be critical for MIR497HG silencing. MIR497HG suppresses cell proliferation, and metastasis by inhibiting YAP, SMAD3, BIRC5, and CCND1 expression (key genes of Hippo/Yap and TGF-b/Smad signaling) [ 28 ].…”

Corrigendum: Silencing of lncRNA MIR497HG via CRISPR/Cas13d Induces Bladder Cancer Progression Through Promoting the Crosstalk Between Hippo/Yap and TGF-β/Smad Signaling

“…Silencing of lncRNA MIR497HG via CRISPR/Cas13d Induces Bladder Cancer Progression Through Promoting the Crosstalk Between Hippo/Yap and TGF-β/Smad Signaling by Zhuang, C., Liu, Y., Fu, S., Yuan, C., Luo, J., Huang, X., Yang, W., Xie, W., Zhuang, C. (2020), Front Mol Biosci. 7:616768. doi: 10.3389/fmolb.2020.616768…”

“…In the original article ( Zhuang et al, 2020 ), there were two errors in Supplementary Figure 2. The “T24 Wound Healing” images of 24 h of “ctrl” in Supplementary Figure 2D and the Supplementary Figure 2F (right) mistakenly used the 5,637 cells data.…”