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Published on: March 30, 2019
circAMOTL1L Suppresses Renal Cell Carcinoma Growth by Modulating the miR-92a-2-5p/KLLN Pathway
Ling Gao1, Xian Shao2, Qingqing Yue3
1Department of Oncology, Kaifeng Central Hospital, Kaifeng, Henan, China.
Abstract:
Accumulating evidence indicates that the dysregulation of circular RNAs (circRNAs) contributes to tumor progression; however, the regulatory functions of circRNAs in renal cell carcinoma (RCC) remain largely unknown. In this study, the function and underlying mechanism of circAMOTL1L in RCC progression were explored. qRT-PCR showed the downregulation of circAMOTL1L in RCC tissues and cell lines. The decrease in circAMOTL1L expression correlated with the tumor stage, metastasis, and poor prognosis in patients with RCC. Functional experiments revealed that circAMOTL1L inhibited cell proliferation and increased apoptosis in RCC cells. Subcutaneous implantation with circAMOTL1L-overexpressing cells in nude mice decreased the growth ability of the xenograft tumors. Mechanistically, circAMOTL1L served as a sponge for miR-92a-2-5p in upregulating KLLN (killin, p53-regulated DNA replication inhibitor) expression validated by bioinformatics analysis, oligo pull-down, and luciferase assays. Further, reinforcing the circAMOTL1L-miR-92a-2-5p-KLLN axis greatly reduced the growth of RCC in vivo. Conclusively, our findings demonstrate that circAMOTL1L has an antioncogenic role in RCC growth by modulating the miR-92a-2-5p-KLLN pathway. Thus, targeting the novel circAMOTL1L-miR-92a-2-5p-KLLN regulatory axis might provide a therapeutic strategy for RCC.
Insights
Circular RNAs (circRNAs) like circAMOTL1L are downregulated in renal cell carcinoma (RCC). circAMOTL1L inhibits RCC progression by regulating the miR-92a-2-5p-KLLN pathway, offering a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) are increasingly implicated in cancer progression.
- The specific roles of circRNAs in renal cell carcinoma (RCC) are not well understood.
Purpose of the Study:
- To investigate the function and mechanism of circAMOTL1L in RCC.
- To determine if circAMOTL1L has a role in tumor suppression in RCC.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) to assess circAMOTL1L expression.
- In vitro cell proliferation and apoptosis assays.
- In vivo xenograft tumor growth studies in nude mice.
- Bioinformatics analysis, oligo pull-down, and luciferase assays to elucidate molecular mechanisms.
Main Results:
- circAMOTL1L was significantly downregulated in RCC tissues and cell lines, correlating with advanced tumor stage, metastasis, and poor prognosis.
- Overexpression of circAMOTL1L suppressed RCC cell proliferation and induced apoptosis.
- circAMOTL1L acted as a molecular sponge for miR-92a-2-5p, leading to the upregulation of KLLN (killin) expression.
- Restoration of the circAMOTL1L-miR-92a-2-5p-KLLN axis inhibited tumor growth in vivo.
Conclusions:
- circAMOTL1L exhibits antioncogenic properties in RCC.
- The circAMOTL1L-miR-92a-2-5p-KLLN pathway is a key regulatory axis in RCC progression.
- This pathway represents a potential therapeutic target for RCC treatment.
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