Ribosomal protein S3 selectively affects colon cancer growth by modulating the levels of p53 and lactate dehydrogenase
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ORIGINAL ARTICLE
Ribosomal protein S3 selectively affects colon cancer growth by modulating the levels of p53 and lactate dehydrogenase Elie Alam1 · Lama Maaliki1 · Zeina Nasr1 Received: 24 June 2019 / Accepted: 26 July 2020 © Springer Nature B.V. 2020
Abstract Ribosomal protein S3 (RPS3) is a component of the 40S ribosomal subunit. It is known to function in ribosome biogenesis and as an endonuclease. RPS3 has been shown to be over expressed in colon adenocarcinoma but its role in colon cancer is still unknown. In this study, we aim at determining the expression levels of RPS3 in a colon cancer cell line Caco-2 compared to a normal colon mucosa cell line NCM-460 and study the effects of targeting this protein by siRNA on cellular behavior. RPS3 was found to be expressed in both cell lines. However, siRNA treatment showed a more protruding effect on Caco-2 cells compared to NCM-460 cells. RPS3 knockdown led to a significant decrease in the proliferation, survival, migration and invasion and an increase in the apoptosis of Caco-2 cells. Western blot analysis demonstrated that these effects correlated with an increase in the level of the tumor suppressor p53 and a decrease in the level and activity of lactate dehydrogenase (LDH), an enzyme involved in the metabolism of cancer cells. No significant effect was shown in normal colon NCM-460 cells. Targeting p53 by siRNA did not affect RPS3 levels indicating that p53 may be a downstream target of RPS3. However, the concurrent knockdown of RPS3 and p53 showed no change in LDH level in Caco-2 cells suggesting an interesting interplay among the three proteins. These findings might present RPS3 as a selective molecular marker in colon cancer and an attractive target for colon cancer therapy. Keywords Ribosmal protein S3 · p53 · Lactate dehydrogenase · Colon cancer · siRNA
Introduction Ribosomal protein S3 (RPS3) is a component of the small ribosomal subunit 40S. It is involved in the 40S ribosomal maturation and initiation of translation through the interaction with various initiation factors like eIF3 and eIF2 [1]. RPS3 plays a role in DNA damage repair due to the presence of its amino acid sequence that is identical to an apurinic/ apyrimidinic endonuclease II [2]. In addition, RPS3 has been shown to have other extraribosomal functions including control of apoptosis, survival, transcription and tumorigenesis [3]. RPS3 is reported to be associated with p53 and MDM2 where its knockdown decreases the high level of p53 when the HEK 293 cells are under oxidative stress [4]. Furthermore, RPS3 silencing promotes ribosomal stress which impairs ribosomal biogenesis and by its turn induces * Zeina Nasr [email protected] 1
Department of Biology, Faculty of Arts and Sciences, University of Balamand, P.O.B. 100, Tripoli, Lebanon
the activation of c-Myc and p38 leading to p53 induction and G1 cell cycle arrest in HT1080 fibrosarcoma cells [5]. The level of mRNA corresponding to RPS3 is shown to be higher in colorectal tumor cells and adenomatous polyps, compared to no
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