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Ribosomal protein S3 selectively affects colon cancer growth by modulating the levels of p53 and lactate dehydrogenase

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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.

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Acknowledgements

This work was supported by the Lebanese National Council for Scientific Research (Grant # CNRS020614). We would also like to acknowledge Dr. Samer Bazzi for performing the flow cytometry experiments.

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  1. Department of Biology, Faculty of Arts and Sciences, University of Balamand, P.O.B. 100, Tripoli, Lebanon

    Elie Alam, Lama Maaliki & Zeina Nasr

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Correspondence to Zeina Nasr.

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Alam, E., Maaliki, L. & Nasr, Z. Ribosomal protein S3 selectively affects colon cancer growth by modulating the levels of p53 and lactate dehydrogenase. Mol Biol Rep 47, 6083–6090 (2020). https://doi.org/10.1007/s11033-020-05683-1

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