Ribosomal protein RPL5 regulates colon cancer cell proliferation and migration through MAPK/ERK signaling pathway.

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS ACS Applied Bio Materials Pub Date : 2022-11-16 DOI:10.1186/s12860-022-00448-z
Huahua Zhang, Junli Liu, Qingqing Dang, Xueru Wang, Jie Chen, Xiaoyin Lin, Na Yang, Juan Du, Haiyan Shi, Yong Liu, Jiming Han
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引用次数: 4

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

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核糖体蛋白RPL5通过MAPK/ERK信号通路调控结肠癌细胞增殖和迁移。
背景:核糖体蛋白的异常表达对肿瘤的发展具有重要的调控作用。RPL5参与多种恶性肿瘤的进展,然而,RPL5在结肠癌中的作用仍不清楚。方法:采用TCGA和GTEx数据库的数据分析RPL5在泛癌组织中的表达。应用western blotting检测RPL5在临床结肠癌组织样本和人结肠癌细胞株中的表达水平;设计靶向RPL5的siRNA,通过western blotting和RT-qPCR验证其干扰效率;采用CCK8法、克隆形成法、细胞周期法、细胞划痕法观察RPL5对结肠癌细胞增殖和迁移的影响;western blotting检测MAPK/ERK信号通路相关蛋白的变化。结果:RPL5在结肠癌组织和细胞系中的表达水平分别显著高于癌旁组织和NCM460细胞,且在HCT116细胞和RKO细胞中的表达水平更高。RPL5的表达抑制了HCT16和RKO细胞的增殖和迁移,使细胞周期停留在G0/G1期。机制研究发现,RPL5下调后,p-MEK1/2、p-ERK、c-Myc表达下调,FOXO3表达上调,ERK激活剂(TBHQ)可部分逆转siRPL5引起的上述作用。此外,TBHQ可以部分逆转siRPL5对结肠癌细胞增殖和迁移的抑制作用。总的来说,RPL5通过激活MAPK/ERK信号通路,至少在一定程度上促进了结肠细胞的增殖和迁移。结论:RPL5通过激活MAPK/ERK信号通路,至少在一定程度上促进了结肠癌细胞的增殖和迁移,这可能成为MAPK/ERK信号通路为主导特征的癌症的新的治疗靶点。
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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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