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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
Apolipoprotein L1 is a tumor suppressor in clear cell renal cell carcinoma metastasis
Linh Nguy-Hoang Le1,2, Cheolwon Choi1, Jae-A Han1
1Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University, Cheonan, Republic of Korea.
Abstract:
The 5-year survival rate of kidney cancer drops dramatically from 93% to 15% when it is metastatic. Metastasis constitutes for 30% of kidney cancer cases, in which clear cell renal cell carcinoma (ccRCC) is the most prominent subtype. By sequencing mRNA of ccRCC patient samples, we found that apolipoprotein L1 (APOL1) was highly expressed in tumors compared to their adjacent normal tissues. This gene has been previously identified in a large body of kidney disease research and was reported as a potential prognosis marker in many types of cancers. However, the molecular function of APOL1 in ccRCC, especially in metastasis, remained unknown. In this study, we modulated the expression of APOL1 in various renal cancer cell lines and analyzed their proliferative, migratory, and invasive properties. Strikingly, APOL1 overexpression suppressed ccRCC metastasis both in vitro and in vivo. We then explored the mechanism by which APOL1 alleviated ccRCC malignant progression by investigating its downstream pathways. APOL1 overexpression diminished the activity of focal adhesive molecules, Akt signaling pathways, and EMT processes. Furthermore, in the upstream, we discovered that miR-30a-3p could inhibit APOL1 expression. In conclusion, our study revealed that APOL1 play a role as a tumor suppressor in ccRCC and inhibit metastasis, which may provide novel potential therapeutic approaches for ccRCC patients.
Insights
Apolipoprotein L1 (APOL1) suppresses clear cell renal cell carcinoma (ccRCC) metastasis. Overexpressing APOL1 reduced tumor cell migration and invasion, suggesting its potential as a therapeutic target for kidney cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Metastatic kidney cancer, particularly clear cell renal cell carcinoma (ccRCC), has a poor 5-year survival rate.
- Apolipoprotein L1 (APOL1) is highly expressed in ccRCC tumors and has been implicated in kidney disease and cancer prognosis.
- The specific role of APOL1 in ccRCC metastasis remained largely uncharacterized.
Purpose of the Study:
- To investigate the molecular function of APOL1 in ccRCC, focusing on its role in metastasis.
- To determine the effect of APOL1 expression modulation on ccRCC cell behavior.
- To elucidate the underlying mechanisms by which APOL1 influences ccRCC progression.
Main Methods:
- Modulation of APOL1 expression in ccRCC cell lines.
- In vitro and in vivo assays to assess proliferative, migratory, and invasive properties.
- Analysis of downstream signaling pathways including focal adhesion molecules, Akt signaling, and epithelial-mesenchymal transition (EMT).
- Investigation of upstream regulators, specifically microRNA-30a-3p (miR-30a-3p).
Main Results:
- APOL1 overexpression significantly suppressed ccRCC metastasis both in vitro and in vivo.
- APOL1 inhibited the activity of focal adhesion molecules, Akt signaling, and EMT processes.
- miR-30a-3p was identified as an inhibitor of APOL1 expression in ccRCC.
Conclusions:
- APOL1 functions as a tumor suppressor in ccRCC, inhibiting metastasis.
- The findings suggest APOL1's potential as a novel therapeutic target for ccRCC patients.
- Understanding the APOL1-miR-30a-3p axis may offer new therapeutic strategies for managing advanced kidney cancer.
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