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Published on: April 7, 2017
Up-regulated microRNA-33b inhibits epithelial-mesenchymal transition in gallbladder cancer through down-regulating
Guohui Xu1, Xiaoyong Wei1, Qiang Tu1
1Department of Hepatobiliary Tumor Surgery, Jiangxi Cancer Hospital, Nanchang 330029, P. R. China.
Abstract:
Gallbladder cancer (GBC) is a relatively rare but fatal gastrointestinal tumor. The microRNA-33b (miR-33b), a member of miR-33 family, is reported to function as a tumor suppressor in various cancers. Notably, miR-33 was predicted to target CROCC based on microarray-based analysis. Hereby, we aimed to characterize the effect of miR-33b on epithelial-mesenchymal transition (EMT) in GBC and the potential mechanism involved with the regulation of CROCC. In GBC cell lines, miR-33b expressed at low levels, and CROCC expressed at high levels, with enhanced EMT process. To further examine the specific mechanism of miR-33b and CROCC in GBC, the GBC cells were treated with the miR-33b mimic/inhibitor or siRNA-CROCC to assess the expression alteration of EMT-related genes and cell proliferation, migration, and invasion. MiR-33b was verified to target and down-regulate the expression of CROCC. The miR-33b up-regulation or CROCC silencing was observed to increase the level of E-cadherin but decrease the levels of N-cadherin and Vimentin, corresponding to impeded cell proliferation, migration, invasion, EMT, and tumor growth. The findings suggest that miR-33b up-regulation hinders GBC development through down-regulating CROCC, which was achieved by inhibition of EMT. The present study may provide an insight on a novel target for GBC treatment.
Insights
MicroRNA-33b (miR-33b) acts as a tumor suppressor in gallbladder cancer (GBC) by down-regulating CROCC. This inhibition impedes epithelial-mesenchymal transition (EMT), hindering GBC progression and offering a potential new treatment target.
Area of Science:
- Oncology
- Molecular Biology
- Gastroenterology
Background:
- Gallbladder cancer (GBC) is a rare but aggressive malignancy.
- MicroRNA-33b (miR-33b) is a known tumor suppressor in various cancers.
- CROCC is a potential target of miR-33b, implicated in cancer progression.
Purpose of the Study:
- To investigate the role of miR-33b in GBC.
- To elucidate the mechanism of miR-33b in regulating epithelial-mesenchymal transition (EMT) in GBC.
- To determine if miR-33b targets CROCC in GBC.
Main Methods:
- GBC cell lines were treated with miR-33b mimics/inhibitors or siRNA targeting CROCC.
- Expression levels of miR-33b, CROCC, and EMT-related genes (E-cadherin, N-cadherin, Vimentin) were assessed.
- Cell proliferation, migration, and invasion assays were performed.
Main Results:
- miR-33b was underexpressed, while CROCC was overexpressed in GBC cells, correlating with enhanced EMT.
- miR-33b was confirmed to target and down-regulate CROCC expression.
- Upregulating miR-33b or silencing CROCC increased E-cadherin and decreased N-cadherin and Vimentin, inhibiting proliferation, migration, invasion, EMT, and tumor growth.
Conclusions:
- miR-33b suppresses GBC development by down-regulating CROCC and inhibiting EMT.
- Targeting the miR-33b/CROCC axis presents a promising therapeutic strategy for GBC.
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