Abstract
RAS p21 protein activator 1 (RASA1), also known as p120-RasGAP, is a RasGAP protein that functions as a signaling scaffold protein, regulating pivotal signal cascades. However, its biological mechanism in renal cell carcinoma (RCC) remains unknown. In the present study, RASA1, F-box/WD repeat-containing protein 7 (FBXW7), and miR-223-3p expression were assessed via quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot. Then, the targeted correlations of miR-223-3p with FBXW7 and RASA1 were verified via a dual-luciferase reporter gene assay. CCK-8, flow cytometry, and Transwell assays were implemented independently to explore the impact of RASA1 on cell proliferation, apoptosis, migration, and cell cycle progression. Finally, the influence of RASA1 on tumor formation in RCC was assessed in vivo through the analysis of tumor growth in nude mice. Results showed that FBXW7 and RASA1 expression were decreased in RCC tissues and cell lines, while miR-223-3p was expressed at a higher level. Additionally, FBXW7 and RASA1 inhibited cell proliferation but facilitated the population of RCC cells in the G0/G1 phase. Altogether, RASA1 may play a key role in the progression of RCC by decreasing miR-223-3p and subsequently increasing FBXW7 expression.
Highlights
Renal cell carcinoma (RCC) is a common cancer with approximately 65,000 new cases each year [1]
In RCC cell lines, we found that RAS p21 protein activator 1 (RASA1) expression was decreased compared to the HK2 cell line (Figure 1B)
14 RasGAPs have been identified in mammals [20], and several of them are epigenetically modified in various cancers [21], including NF1 [22], DAB2IP [23], RASAL1 [24], and RASAL2 [25]
Summary
Renal cell carcinoma (RCC) is a common cancer with approximately 65,000 new cases each year [1]. RCC makes up 2–3% of all adult cancers and ranks eighth among the most common causes of death associated with cancers [2]. In addition to its RasGAP domain, RASA1 has two Src homology 2 (SH2) domains, an SH3 domain, a Pleckstrin homology (PH) domain, and a Calcium-dependent phospholipid-binding (C2) domain. It functions as a signaling scaffold protein regulating pivotal signal cascades [8,9]. RASA1 has been implicated in many biological processes including actin filament polymerization, blood vessel development, and cell apoptosis and movement [10].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
