Medical Research and Experimental Center, Medical College, Yan'an University, Yan'an, 716000, China.
Surgical anesthesiology, Yan'an People's Hospital, Yan'an, 716000, China.
BMC Mol Cell Biol. 2022 Nov 16;23(1):48. doi: 10.1186/s12860-022-00448-z.
Abnormal expression of ribosomal proteins has an important regulatory effect on the progression of cancer. RPL5 is involved in the progression of various malignancies, however, the role of RPL5 in colon cancer remains is still unclear.
Data from TCGA and GTEx databases were used to analyze the RPL5 expression in pan-cancer. The expression level of RPL5 in clinical colon cancer tissue samples and human colon cancer cell lines was detected by western blotting; siRNA targeting RPL5 was designed, and its interference efficiency was verified by western blotting and RT-qPCR; CCK8 assay, clone formation assay, cell cycle assay, and cell scratch assay were used to observe the effect of RPL5 on colon cancer cell proliferation and migration; the changes of proteins related to MAPK/ERK signaling pathway were also detected using western blotting.
The expression level of RPL5 in colon cancer tissues and cell lines was significantly higher than that in adjacent tissues and NCM460 cells, respectively, and its expression level was higher in HCT116 cells and RKO cells. Knockdown of RPL5 significantly inhibited the proliferation and migration of HCT16 and RKO cells, and arrested the cell cycle in G0/G1 phase. Mechanistic studies revealed that the expression of p-MEK1/2, p-ERK, c-Myc were down-regulated, and the expression of FOXO3 was up-regulated after down-regulation of RPL5, ERK activator (TBHQ) could partially reverse the above-mentioned effects caused by siRPL5. Moreover, TBHQ could partially reverse the inhibitory effect of siRPL5 on the proliferation and migration of colon cancer cells. Collectively, RPL5 promoted colon cell proliferation and migration, at least in part, by activating the MAPK/ERK signaling pathway.
RPL5 promoted colon cell proliferation and migration, at least in part, by activating the MAPK/ERK signaling pathway, which may serve as a novel therapeutic target for cancers in which MAPK/ERK signaling is a dominant feature.
核糖体蛋白的异常表达对癌症的进展有重要的调节作用。RPL5 参与了各种恶性肿瘤的进展，然而，RPL5 在结肠癌中的作用仍不清楚。
使用 TCGA 和 GTEx 数据库分析 RPL5 在泛癌中的表达。通过 Western blot 检测 RPL5 在临床结肠癌组织样本和人结肠癌细胞系中的表达水平；设计靶向 RPL5 的 siRNA，并通过 Western blot 和 RT-qPCR 验证其干扰效率；CCK8 assay、克隆形成assay、细胞周期assay 和细胞划痕assay 用于观察 RPL5 对结肠癌细胞增殖和迁移的影响；还通过 Western blot 检测 MAPK/ERK 信号通路相关蛋白的变化。
RPL5 在结肠癌组织和细胞系中的表达水平明显高于相邻组织和 NCM460 细胞，在 HCT116 细胞和 RKO 细胞中表达水平更高。敲低 RPL5 显著抑制 HCT16 和 RKO 细胞的增殖和迁移，并将细胞周期阻滞在 G0/G1 期。机制研究表明，下调 RPL5 后，p-MEK1/2、p-ERK、c-Myc 的表达下调，FOXO3 的表达上调，ERK 激活剂（TBHQ）可部分逆转 siRPL5 引起的上述效应。此外，TBHQ 可部分逆转 siRPL5 对结肠癌细胞增殖和迁移的抑制作用。综上所述，RPL5 通过激活 MAPK/ERK 信号通路促进结肠细胞的增殖和迁移，至少部分是这样。
RPL5 通过激活 MAPK/ERK 信号通路促进结肠细胞的增殖和迁移，至少部分是这样，这可能成为 MAPK/ERK 信号为主要特征的癌症的新治疗靶点。
