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Published on: October 27, 2020
TGF-β1 alters microRNA profile in human gastric cancer cells
Haiyan Zhou1, Kuansong Wang, Zhongliang Hu
1Department of Pathology, Xiang-ya School of Medicine, Central South University, Changsha 410013, China.
Objective:
MicroRNAs (miRNAs) are important regulators that play a key role in tumorigenesis and tumor progression. Transforming growth factor-β1 (TGF-β1) is involved in invasion and metastasis in many tumors. In this study, we investigated the microRNAs (miRNA) profiles altered by TGF-β1 in gastric cancer (GC) cells.
Methods:
We detected the expression profiles of miRNA by miRNA microarray and quantitative real-time polymerase chain reaction. Migration and invasion, wound-healing assay, prediction of miRNA targets, Western blot and qRT-PCR analysis were carried out to determine the role of one selected miRNA, namely miR-193b, in affecting the biological behaviors of GC BGC823 cells.
Results:
Among 847 human miRNAs in the microarray, three miRNAs (miR-27a, miR-29b-1 and miR-194) were up-regulated and three (miR-574-3p, miR-193b and miR-130b) were down-regulated in BGC823 cells treated with TGF-β1 compared with control. miR-193b suppressed the invasion and metastasis of GC cells in vivo and in vitro, and down-regulated urokinase-type plasminogen activator (uPA) protein in GC cells.
Conclusions:
TGF-β1 altered miRNA expression profile in BGC823 cells. Among the altered miRNAs, TGF-β1 induced the down-regulation of miR-193b, which inhibited cell invasion and metastasis in vivo and in vitro, and down-regulated uPA protein in GC cells.
Insights
Transforming growth factor-β1 (TGF-β1) alters microRNA (miRNA) profiles in gastric cancer cells. Down-regulation of miR-193b by TGF-β1 inhibits cancer cell invasion and metastasis.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- MicroRNAs (miRNAs) are key regulators in tumorigenesis and cancer progression.
- Transforming growth factor-β1 (TGF-β1) is implicated in tumor invasion and metastasis.
Purpose of the Study:
- To investigate miRNA expression profiles altered by TGF-β1 in gastric cancer (GC) cells.
- To determine the functional role of specific altered miRNAs in GC biological behaviors.
Main Methods:
- miRNA expression profiling using microarray and quantitative real-time polymerase chain reaction (qRT-PCR).
- Assessment of cell migration, invasion, and wound healing.
- Target prediction, Western blot, and qRT-PCR to validate miRNA function.
Main Results:
- TGF-β1 treatment altered the expression of six miRNAs in BGC823 GC cells.
- miR-193b was significantly down-regulated by TGF-β1.
- Overexpression of miR-193b suppressed GC cell invasion and metastasis in vitro and in vivo, and reduced urokinase-type plasminogen activator (uPA) protein levels.
Conclusions:
- TGF-β1 significantly impacts the miRNA expression profile in gastric cancer cells.
- TGF-β1-induced down-regulation of miR-193b contributes to GC cell invasion and metastasis.
- miR-193b acts as a tumor suppressor by inhibiting invasion and metastasis, partly through regulating uPA.
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