Death-inducer obliterator 1 (DIDO1) silencing suppresses growth of bladder cancer cells through decreasing SAPK/JNK signaling cascades.

Abstract

Death inducer obliterator (DIDO) is involved in apoptosis and embryonic stem cell self-renewal. Here, we investigate the effect of DIDO1 on bladder cancer cells and clarify the underlying molecular mechanism. Bladder cancer tissues and cell lines (T24, ScaBER, 5637), as well as normal bladder epithelial cells (SV-HUC-1), were used to measure the levels of DIDO1 mRNA and protein by qRT-PCR and western blot, respectively. The results indicated that DIDO1 was highly expressed in bladder cancer tissues and cell lines. And the expression of DIDO1 in T24 and 5637 cells was higher than that in ScaBER and SV-HUC-1 cells. The expression of DIDO1 was knocked down in T24 and 5637 cells by infection with shDIDO1-1 and shDIDO1-2 lentivirus. The growth of T24 and 5637 cells was monitored using Celigo, MTT assays, and colony formation assay. Apoptosis was examined by flow cytometric analysis. The effect of DIDO1 knockdown on tumorigenesis of T24 xenograft tumors was determined in nude mice. Reduction of DIDO1 mRNA resulted in reduced proliferation, decreased cell colony formation, increased apoptosis in vitro, and inhibited tumorigenesis in vivo. Furthermore, we identified signaling molecules involved in stress and apoptosis using the PathScan Antibody Array Kit and western blot. The depletion of DIDO1 significantly decreased the levels of phosphorylated SAPK/JNK, and Chk1/2, as well as the upregulating cleaved Caspase-7 expression. These results indicated that the potential mechanism of DIDO1 action might involve SAPK/JNK signaling cascades.

• Authors: J Li, A Sheng Wang, S Wang, C Yong Wang, S Xue, W Yong Li, T Tu Ma, Y Xi Shan
• Journal: Neoplasma (Neoplasma) Vol. 67 Issue 5 Pg. 1074-1084 (Sep 2020) ISSN: 0028-2685 [Print] Slovakia
• PMID: 32484699 (Publication Type: Journal Article)

Chemical References

• DNA-Binding Proteins
• Dido protein, mouse
• Transcription Factors

Topics

• Animals
• Apoptosis
• Cell Line, Tumor
• Cell Proliferation
• DNA-Binding Proteins (genetics)
• Epithelial Cells
• Gene Knockdown Techniques
• Gene Silencing
• Humans
• MAP Kinase Signaling System
• Mice
• Mice, Nude
• Neoplasm Transplantation
• Transcription Factors (genetics)
• Urinary Bladder Neoplasms (genetics, pathology)