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miR-93 functions as an oncomiR for the downregulation of PDCD4 in gastric carcinoma
Hongwei Liang1, Feng Wang2, Danping Chu1
1State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute for Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Science, Nanjing University, Nanjing, Jiangsu 210093, China.
Abstract:
Programmed cell death 4 (PDCD4), as a tumor suppressor gene, is frequently reduced in a variety of tumors, including gastric cancer. Previous findings have indicated that PDCD4 participates in tumorigenesis through the regulation of apoptosis, but the molecular basis of this process has not been fully elucidated, and no studies have shown the upstream regulation of this gene in gastric cancer. In this study, we used bioinformatics analysis to search for miRNAs that could potentially target PDCD4 and identified miR-93 as a candidate. Moreover, we observed the inverse correlation between miR-93 and PDCD4 protein levels, but not mRNA levels, in human gastric cancer tissues. We further experimentally validated PDCD4 as the direct target of miR-93 by evaluating PDCD4 expression in gastric cancer cells after the overexpression or knockdown of miR-93. Additionally, the biological consequences of targeting PDCD4 through miR-93 were examined using cell apoptosis assays in vitro. We demonstrated that the repression of PDCD4 through miR-93 suppressed the apoptosis of gastric cancer cells. Finally, we revealed that miR-93 promoted the development of gastric tumor growth in xenograft mice by negatively regulating PDCD4. Taken together, the findings of the present study indicated the oncogenic role of miR-93 in gastric cancer tumorigenesis through targeting PDCD4, particularly in apoptosis.
Insights
MicroRNA-93 (miR-93) promotes gastric cancer by suppressing the tumor suppressor programmed cell death 4 (PDCD4). This leads to reduced apoptosis and increased tumor growth, highlighting miR-93 as an oncogenic factor in gastric cancer.
Area of Science:
- Molecular Biology
- Oncology
- Gene Regulation
Background:
- Programmed cell death 4 (PDCD4) is a tumor suppressor frequently downregulated in gastric cancer, impacting apoptosis and tumorigenesis.
- The upstream regulatory mechanisms of PDCD4 in gastric cancer remain largely uncharacterized.
Purpose of the Study:
- To investigate the role of microRNAs (miRNAs) in regulating PDCD4 expression in gastric cancer.
- To elucidate the molecular mechanism by which miR-93 influences gastric cancer progression.
Main Methods:
- Bioinformatic analysis to identify potential miRNA targets of PDCD4.
- Correlation analysis of miR-93 and PDCD4 protein/mRNA levels in gastric cancer tissues.
- Experimental validation of miR-93 targeting PDCD4 using cell lines (overexpression/knockdown).
- In vitro apoptosis assays and in vivo xenograft mouse models to assess tumor growth.
Main Results:
- miR-93 was identified as a direct targeting miRNA of PDCD4.
- An inverse correlation was observed between miR-93 and PDCD4 protein levels in gastric cancer tissues.
- Overexpression of miR-93 suppressed PDCD4 expression, leading to reduced apoptosis in gastric cancer cells.
- miR-93 promoted gastric tumor growth in vivo by negatively regulating PDCD4.
Conclusions:
- miR-93 acts as an oncogenic factor in gastric cancer by targeting and downregulating the tumor suppressor PDCD4.
- The miR-93/PDCD4 axis plays a critical role in regulating apoptosis and promoting gastric tumor development.
- Targeting miR-93 may represent a potential therapeutic strategy for gastric cancer.
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