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Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
MiR-19b suppresses PTPRG to promote breast tumorigenesis
Minghui Liu1, Rong Yang1,2, Uzair Urrehman1
1State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210046, China.
Abstract:
Protein tyrosine phosphatase receptor type G (PTPRG) is an important tumor suppressor gene in multiple human cancers. In this study, we found that PTPRG protein levels were downregulated in breast cancer tissues while the mRNA levels varied irregularly, implying a post-transcriptional mechanism was involved. Because microRNAs are powerful post-transcriptional regulators of gene expression, we used bioinformatics analysis to search for microRNAs that potentially targets PTPRG in the setting of breast cancer. We identified two specific binding sites for miR-19b in the 3'-untranslated region of PTPRG. We further identified an inverse correlation between miR-19b and PTPRG protein levels, but not mRNA levels, in human breast cancer tissues. By overexpressing or knocking down miR-19b in MCF-7 cells and MDA-231 cells, we experimentally confirmed that miR-19b directly suppresses PTPRG expression. Furthermore, we determined that the inhibition of PTPRG by miR-19b leads to increased proliferation, stimulated cell migration and reduced apoptosis. Taken together, our findings provide the first evidence that miR-19b inhibits PTPRG expression to promote tumorigenesis in human breast cancer.
Insights
MicroRNA-19b (miR-19b) promotes breast cancer by downregulating the tumor suppressor Protein tyrosine phosphatase receptor type G (PTPRG). This study reveals miR-19b as a key regulator in breast cancer progression.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Protein tyrosine phosphatase receptor type G (PTPRG) functions as a tumor suppressor in various human cancers.
- Downregulation of PTPRG protein in breast cancer tissues suggests post-transcriptional regulation.
Purpose of the Study:
- To investigate the role of microRNAs in regulating PTPRG expression in breast cancer.
- To identify specific microRNAs targeting PTPRG and elucidate their functional impact on tumorigenesis.
Main Methods:
- Bioinformatic analysis to predict microRNA binding sites on PTPRG.
- Correlation analysis of miR-19b and PTPRG levels in human breast cancer tissues.
- In vitro experiments involving overexpression and knockdown of miR-19b in breast cancer cell lines (MCF-7 and MDA-231).
Main Results:
- Two binding sites for miR-19b were identified in the 3'-untranslated region of PTPRG.
- An inverse correlation was observed between miR-19b and PTPRG protein levels, but not mRNA levels.
- miR-19b was confirmed to directly suppress PTPRG expression, leading to increased cell proliferation, migration, and reduced apoptosis.
Conclusions:
- miR-19b acts as an oncogenic microRNA in breast cancer by inhibiting the tumor suppressor PTPRG.
- The miR-19b/PTPRG axis plays a significant role in promoting breast cancer progression.
- Targeting miR-19b may represent a potential therapeutic strategy for breast cancer.
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