RASAL2 suppresses the proliferative and invasive ability of PC3 prostate cancer cells
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Krishma Tailor1, Joseph Paul1, Somiranjan Ghosh2, Namita Kumari3 and Bernard Kwabi-Addo1
1 Department of Biochemistry and Molecular Biology, Howard University, Washington, DC 20059, USA
2 Department of Biology, Howard University, Washington, DC 20059, USA
3 Center for Sickle Cell Disease, Howard University, Washington, DC 20059, USA
|Bernard Kwabi-Addo,||email:||[email protected]|
Keywords: RASAL2; Ras-protooncogene; prostate cancer; TNFα signal; DNA methylation
Received: September 11, 2021 Accepted: December 08, 2021 Published: December 21, 2021
The RAS protein activator like 2 (RASAL2) negatively regulates RAS proto-oncogene which is activated by high mutation rate in cancer. Thus, RASAL2 expression could potentially limit the function of RAS in prostate cancer (PCa). Genome-wide DNA methylation analysis demonstrated that RASAL2 is differentially hypermethylated in PCa tissues compared to benign prostate tissues. The PCR analysis of RASAL2 mRNA transcript showed differential expression in a panel of prostate cell lines with most PCa showing lower RASAL2 expression compared to benign prostatic epithelial cells. In PCa PC3 cells, the ectopic expression of RASAL2 significantly inhibited cell proliferation and invasion and induced an S phase plus G2/M phase cell cycle arrest. Ingenuity Pathway Analysis (IPA) demonstrated a cross talk between RASAL2 and TNFα, a key cytokine in immune signaling pathway that is relevant in PCa. Over-expression of RASAL2 downregulated TNFα expression whereas the knockdown of RASAL2 caused increased expression of TNFα. Taken together, our data demonstrates tumor suppressor role for RASAL2 in human PCa cells, despite increased RAS oncogenic activity. Our observation provides a new mechanistic insight of RASAL2 expression in aberrant Ras expression and immune signaling in PCa cells suggesting a potential novel therapeutic target for PCa.
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