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Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
Published on: February 8, 2020
FOXM1-Activated LINC01094 Promotes Clear Cell Renal Cell Carcinoma Development via MicroRNA 224-5p/CHSY1
Yufeng Jiang1, Haimin Zhang2, Wei Li3
1Department of Urology, Chongming Branch, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
Abstract:
Clear cell renal cell carcinoma (ccRCC) is regarded as the most aggressive subtype of RCC, with high rates of metastasis and recurrence. An extensive body of studies had proved long noncoding RNAs (lncRNAs) play pivotal parts in the development and evolution of diverse malignant tumors. However, the potential of LINC01094 in ccRCC tumorigenesis is still unexplored. In the present research, with the aid of the TCGA database, we found that LINC01094 was highly expressed in ccRCC tissues. Upregulation of LINC01094 was also confirmed in ccRCC cell lines, and functional experiments delineated that LINC01094 knockdown led to inhibition on ccRCC cell growth and metastasis. Moreover, LINC01094 was activated by FOXM1 at the transcriptional level. Further assay demonstrated that LINC01094 worked as a sponge of microRNA 224-5p (miR-224-5p) and CHSY1 was a miR-224-5p-targeted mRNA. Further, we verified that LINC01094 acted as a competing endogenous RNA in ccRCC to regulate CHSY1 expression via competitively bind to miR-224-5p. Lastly, our results expounded that LINC01094 exerted its tumor-promoting performance in ccRCC development through miR-224-5p/CHSY1 regulatory axis, which shed light on the molecular mechanism underlying LINC01094 in ccRCC and opened a new prospective for the treatment of ccRCC.
Insights
Long noncoding RNA LINC01094 promotes clear cell renal cell carcinoma (ccRCC) growth and metastasis by regulating the miR-224-5p/CHSY1 axis. This finding offers new therapeutic targets for ccRCC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Clear cell renal cell carcinoma (ccRCC) is an aggressive kidney cancer subtype with high metastasis and recurrence rates.
- Long noncoding RNAs (lncRNAs) are implicated in various cancers, but LINC01094's role in ccRCC remains unclear.
Purpose of the Study:
- To investigate the role and molecular mechanism of LINC01094 in ccRCC tumorigenesis.
Main Methods:
- Utilized TCGA database for expression analysis.
- Performed functional experiments (knockdown) in ccRCC cell lines.
- Investigated regulatory interactions involving LINC01094, FOXM1, miR-224-5p, and CHSY1.
Main Results:
- LINC01094 was significantly upregulated in ccRCC tissues and cell lines.
- LINC01094 knockdown inhibited ccRCC cell proliferation and metastasis.
- LINC01094 acts as a competing endogenous RNA (ceRNA) by sponging miR-224-5p, thereby upregulating CHSY1 expression, and is transcriptionally activated by FOXM1.
Conclusions:
- LINC01094 promotes ccRCC development via the miR-224-5p/CHSY1 axis.
- LINC01094 represents a potential therapeutic target for ccRCC.
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