Activation of the ribosomal protein L13 gene in human gastrointestinal cancer

Abstract

Abstract. Although ribosomal proteins are major components of ribosomes, recent data have shown them to have extraribosomal functions apart from ribosome and protein biosynthesis. In our earlier study, we showed that ribosomal protein L13 mRNA was up-regulated in response to DNA damage in hamster cells. We report here that L13 expression is up-regulated in human gastrointestinal cancers. We also examined the biological role of L13 on human cancer cells. Knocking down L13 expression using small interfering RNA (siRNA) resulted in drastic attenuation of cancer cell growth with significant G1 and G2/M arrest of the cell cycle. Moreover, L13 siRNA significantly enhanced the cellular sensitivity to certain DNA damaging agents and, concordantly, L13-overexpressing cells demonstrated greater chemoresistance compared to parent cells, suggesting an inverse correlation between L13 expression and chemosensitivity. By using semiquantitative RT-PCR, we analyzed expression of L13 in freshly resected cancer tissue of the stomach, colorectum and liver. Up-regulation of L13 mRNA expression was observed in 10 (28%) of 36 gastric, 19 (41%) of 46 colorectal and 5 (20%) of 25 liver cancer tissue samples compared to adjacent normal tissue samples. We also found that increased expression of the L13 gene correlated with clinical staging in gastric cancers. The results of this study suggest that L13 plays an essential role in the progression of some gastrointestinal malignancies.

Identification of TTP mRNA targets in human dendritic cells reveals TTP as a critical regulator of dendritic cell maturation

“…There are seven different S27 message isoforms all with identical coding regions but different tissue distributions, consistent with post-transcriptional regulation (Thomas et al 2000). Ribosomal proteins L7 and S11 are overexpressed in colorectal carcinomas (Kasai et al 2003), while the L13 protein, which has an identical protein-coding region to the breast basic conserved 1 protein (BBC1), is overexpressed in gastrointestinal cancer cells (Kobayashi et al 2006). RNAi knockdown of L13 significantly enhanced the sensitivity of these cells to DNA damage, while exogenous addition of L13 expression into cells inhibited chemosensitivity (Kobayashi et al 2006).…”

“…Ribosomal proteins L7 and S11 are overexpressed in colorectal carcinomas (Kasai et al 2003), while the L13 protein, which has an identical protein-coding region to the breast basic conserved 1 protein (BBC1), is overexpressed in gastrointestinal cancer cells (Kobayashi et al 2006). RNAi knockdown of L13 significantly enhanced the sensitivity of these cells to DNA damage, while exogenous addition of L13 expression into cells inhibited chemosensitivity (Kobayashi et al 2006). Finally, a recent report identified several ribosomal proteins as specific markers of juvenile idiopathic arthritis (Allantaz et al 2007).…”

The role of ribosomal proteins in the regulation of cell proliferation, tumorigenesis, and genomic integrity

“…Indeed, some RPs have been found to be up-regulated in human cancer tissues, as compared to adjacent normal tissues (Table 3). For example, up-regulation of L13 mRNA expression was observed in 10 of 36 (28%) gastric, 19 of 46 (41%) colorectal and 5 of 25 (20%) liver cancer tissues compared to their corresponding adjacent normal tissues (Kobayashi et al, 2006). Moreover, high expression of L13 is correlated with later staging of gastric cancers (Kobayashi et al, 2006).…”

“…Activated p53 then transactivates its downstream targets to induce growth arrest and apoptosis to block tumorigenesis. (Adilakshmi and Laine, 2002;Bai et al, 2014;Barlow et al, 2010a;He and Sun, 2007;Jang et al, 2012a;Jeon et al, 2008;Khanna et al, 2003;Li et al, 2010;Naora et al, 1998;Neumann and Krawinkel, 1997;Russo et al, 2013;Takagi et al, 2005;Wu et al, 2012;Yang et al, 2012;Zhu et al, 2009) Cell cycle S3, S5, S6, S7, S14, S15, S19, S20, S25, S26, S27, S27L, S27a, L3, L5, L6, L7, L11, L13, L23, L26, L31, L34, L37, L41 (Cui et al, 2014;Daftuar et al, 2013;Dai et al, , 2007bGao et al, 2013;Gou et al, 2010;Iadevaia et al, 2010;Kobayashi et al, 2006;Maruyama et al, 2014;Matragkou et al, 2008;Moorthamer and Chaudhuri, 1999;Neumann and Krawinkel, 1997;Russo et al, 2013;Sun et al, 2011;Takagi et al, 2005;Wang et al, 2011a;Wanzel et al, 2008;Xiong et al, 2011;Zhang et al, 2013Zhang et al, , 2015Zhou et al, 2013a) Cell proliferation S6, S9, S13, S14, S15a, S24, S27, L6, L8, L11, L15, L17, L26, L29, L31, L34, L36a (Dai et al, 2007a;Gou et al, 2010Kim et al, 2004;Li et al, 2010…”

“…For example, up-regulation of L13 mRNA expression was observed in 10 of 36 (28%) gastric, 19 of 46 (41%) colorectal and 5 of 25 (20%) liver cancer tissues compared to their corresponding adjacent normal tissues (Kobayashi et al, 2006). Moreover, high expression of L13 is correlated with later staging of gastric cancers (Kobayashi et al, 2006). The elevated expression of L19 is associated with prostatic malignancy, and more importantly, poor survival of prostate cancer patients (Bee et al, 2006).…”