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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
LINC01426 contributes to clear cell renal cell carcinoma progression by modulating CTBP1/miR-423-5p/FOXM1 axis via
YuFeng Jiang1, HaiMin Zhang2, Wei Li2
1Department of Urology, Chongming Branch, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
Abstract:
Increasing evidence suggests that long noncoding RNAs (lncRNAs) are pivotal regulators in oncogenesis. However, the role of numerous lncRNAs has never been unmasked in clear cell renal cell carcinoma (ccRCC). Presently, we investigated the function of long intergenic nonprotein coding RNA 1426 (LINC01426) in ccRCC, as The Cancer Genome Atlas data indicated that LINC01426 was highly expressed in ccRCC tissues and its overexpression was correlated with disappointing prognosis. First, we verified that LINC01426 was indeed upregulated in ccRCC cell lines and its depletion restrained ccRCC cell proliferation and migration. Besides, we proved that LINC01426 facilitated ccRCC tumorigenesis via forkhead box M1 (FOXM1). Moreover, it was revealed that miR-423-5p was downregulated and directly targeted FOXM1 in ccRCC, and that LINC01426 positively regulated FOXM1 via its inhibition on miR-423-5p. Notably, we also uncovered that miR-423-5p was transcriptionally silenced by CTBP1 and HDAC2. Of importance, LINC01426 was certified to distribute both in the cytoplasm and the nucleus of ccRCC cells, and it increased CTBP1 expression through recruiting insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) in cytoplasm whereas interacted with CTBP1 protein to improve the transcriptional repression on miR-423-5p in nucleus. Jointly, our observations unveiled that LINC01426 aggravates ccRCC progression via IGF2BP1/CTBP1/HDAC2/miR-423-5p/FOXM1 axis, highlighting LINC01426 as a novel promising target for ccRCC treatment.
Insights
Long intergenic nonprotein coding RNA 1426 (LINC01426) promotes clear cell renal cell carcinoma (ccRCC) progression by regulating the IGF2BP1/CTBP1/HDAC2/miR-423-5p/FOXM1 axis. This study identifies LINC01426 as a potential therapeutic target for ccRCC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Long noncoding RNAs (lncRNAs) play critical roles in oncogenesis.
- The specific functions of many lncRNAs in clear cell renal cell carcinoma (ccRCC) remain largely unknown.
- The Cancer Genome Atlas data suggests LINC01426 is highly expressed in ccRCC and linked to poor prognosis.
Purpose of the Study:
- To investigate the role and mechanism of long intergenic nonprotein coding RNA 1426 (LINC01426) in ccRCC.
- To elucidate the regulatory axis involving LINC01426, miR-423-5p, and FOXM1 in ccRCC.
- To identify LINC01426 as a potential therapeutic target for ccRCC.
Main Methods:
- Analysis of The Cancer Genome Atlas data for LINC01426 expression in ccRCC.
- Experimental validation of LINC01426 upregulation in ccRCC cell lines.
- Assessment of LINC01426 depletion effects on ccRCC cell proliferation and migration.
- Investigation of the interaction between LINC01426, miR-423-5p, FOXM1, CTBP1, HDAC2, and IGF2BP1 using molecular biology techniques.
Main Results:
- LINC01426 is upregulated in ccRCC and its depletion inhibits cell proliferation and migration.
- LINC01426 promotes ccRCC tumorigenesis by regulating the FOXM1 pathway.
- LINC01426 positively regulates FOXM1 by inhibiting miR-423-5p, which is transcriptionally silenced by CTBP1 and HDAC2.
- LINC01426 interacts with IGF2BP1 and CTBP1 to modulate miR-423-5p expression in both cytoplasm and nucleus, ultimately promoting ccRCC progression.
Conclusions:
- LINC01426 exacerbates ccRCC progression through the IGF2BP1/CTBP1/HDAC2/miR-423-5p/FOXM1 axis.
- LINC01426 represents a novel and promising therapeutic target for ccRCC.
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