Knockdown of circSMAD2 inhibits the tumorigenesis of gallbladder cancer through binding with eIF4A3

Abstract

Background Gallbladder cancer (GBC) is the seventh most common gastrointestinal cancer worldwide. This study aimed to investigate the function of circSMAD2 in GBC. Methods To investigate the function of circSMAD2 in GBC, the level of circSMAD2 in GBC cells was detected by RT-qPCR. CCK-8 assay was performed to investigate the cell viability. Cell apoptosis was tested by flow cytometry. In addition, transwell assay was used to detect the cell migration and invasion. RIP and RNA pull-down were used to explore the relation among circSMAD2, eIF4A3 and SMAD2. Meanwhile, xenograft mice model was established to investigate the function of circSMAD2 in GBC. Results The data revealed that circSMAD2 was upregulated in GBC, and circSMAD2 knockdown significantly inhibited the viability of GBC cells. In addition, circSMAD2 siRNA notably induced the apoptosis in GBC cells. The migration and invasion of GBC cells were obviously suppressed in the presence of circSMAD2 siRNA. Meanwhile, circSMAD2 suppressed the binding between eukaryotic translation initiation factor 4A3 (eIF4A3) and SMAD2 through binding with eIF4A3. Knockdown of circSMAD2 notably inhibited the expression of SMAD2 in GBC cells, and SMAD2 overexpression partially reversed the anti-tumor effect of circSMAD2 knockdown. Finally, circSMAD2 siRNA significantly inhibited the tumor growth of GBC in vivo. Conclusion Knockdown of circSMAD2 inhibits the tumorigenesis of gallbladder cancer through binding with eIF4A3. Thus, our study provided a new strategy for the treatment of GBC.

Inhibition of circRNA NGFR promotes ferroptosis in gallbladder carcinoma cells

“…FOXP1 enhances GBC progression via PKLR signaling [ 25 ], and circRNAs are involved in the promotion of GBC. Researchers have suggested that inhibition of circRNA SMAD2 suppresses the growth of GBC through eIF4A3 [ 26 ]. However, there are few reports on the role of the circRNA NGFR in GBC development.…”

CircRNA and ferroptosis in human disease: Insights for new treatments

“…13 Additional research showed that circSMAD2 can inhibit the binding of eukaryotic translation initiation factor 4A3 (EIF4A3) to SMAD2 by binding to EIF4A3, thereby affecting the progression of gallbladder cancer. 14 Yuan et al found that hsa_circ_0072309 promotes autophagy among glioblastoma cells and increases their sensitivity to temozolomide through a P53-dependent mechanism. 15 Furthermore, circRNAs have been used to help diagnose disease based on liquid biopsies of tumors.…”

“…Down‐regulation of circRNA_010383 promotes the accumulation of extracellular matrix (ECM) proteins, promoting proteinuria, and renal fibrosis in patients with diabetic nephropathy, and can be used as a therapeutic target for diabetic nephropathy 13 . Additional research showed that circSMAD2 can inhibit the binding of eukaryotic translation initiation factor 4A3 (EIF4A3) to SMAD2 by binding to EIF4A3, thereby affecting the progression of gallbladder cancer 14 . Yuan et al.…”