RNA-binding protein RPS7 promotes hepatocellular carcinoma progression via LOXL2-dependent activation of ITGB1/FAK/SRC signaling

作者全名："Zhou, Yu-Jiao; Yang, Min-Li; He, Xin; Gu, Hui-Ying; Ren, Ji-Hua; Cheng, Sheng-Tao; Fu, Zhou; Zhang, Zhen-Zhen; Chen, Juan"

作者地址："[Zhou, Yu-Jiao; Zhang, Zhen-Zhen] Chongqing Med Univ, Childrens Hosp, Natl Clin Res Ctr Child Hlth & Disorders, Minist Educ,Key Lab Child Dev & Disorders,Chongqin, 20 Jinyu Rd, Yubei Dist, Chongqing 401122, Peoples R China; [Yang, Min-Li; He, Xin; Gu, Hui-Ying; Ren, Ji-Hua; Cheng, Sheng-Tao; Chen, Juan] Chongqing Med Univ, Key Lab Mol Biol Infect Dis Designated, Chinese Minist Educ, Chongqing, Peoples R China; [Fu, Zhou] Chongqing Med Univ, Childrens Hosp, Key Lab Child Dev & Disorders, Stem Cell Biol & Therapy Lab,Minist Educ, Chongqing 400046, Peoples R China; [Fu, Zhou] Chongqing Med Univ, Childrens Hosp, Dept Resp Dis, Chongqing, Peoples R China; [Chen, Juan] Chongqing Med Univ, Key Lab Lab Med Diagnost, Chinese Minist Educ, 1 Youyi Rd, Chongqing 400016, Peoples R China"

通信作者："Zhang, ZZ (通讯作者)，Chongqing Med Univ, Childrens Hosp, Natl Clin Res Ctr Child Hlth & Disorders, Minist Educ,Key Lab Child Dev & Disorders,Chongqin, 20 Jinyu Rd, Yubei Dist, Chongqing 401122, Peoples R China.; Chen, J (通讯作者)，Chongqing Med Univ, Key Lab Mol Biol Infect Dis Designated, Chinese Minist Educ, Chongqing, Peoples R China.; Chen, J (通讯作者)，Chongqing Med Univ, Key Lab Lab Med Diagnost, Chinese Minist Educ, 1 Youyi Rd, Chongqing 400016, Peoples R China."

来源：JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001157689800001

JCR分区：Q1

影响因子：11.4

年份：2024

卷号：43

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Hepatocellular carcinoma; RNA-binding protein; Ribosomal protein S7; Lysyl oxidase-like 2; Focal adhesion; Metastasis

摘要："BackgroundMetastasis is one of the leading cause contributes to treatment failure and poor prognosis of hepatocellular carcinoma (HCC) patients. The underlying mechanism of HCC metastasis remains to be determined. Although several RNA binding proteins (RBPs) have been found to participate in tumorigenesis and progression of liver cancer, the role of RBPs in HCC patients with extrahepatic metastases is poorly understood.MethodsBy performing RNA-seq of primary HCC tissues (including HCC with extrahepatic metastasis and those did not develop metastasis), we identified a set of HCC metastasis-associated RBPs candidates. Among which, ribosomal protein S7 (RPS7) was found to be remarkably increased in HCC tissues and be strongly related to HCC poor survival. Overexpression or CRISPR-Cas9-mediated knockout were applied to investigate the role of RPS7 on the metastasis-associated phenotypes of HCC cells. RNA sequencing, RIP, RNA-pull down, dual luciferase reporter assay, nascent RNA capture assay, and RNA decay and so on, were applied to reveal the underlying mechanism of RPS7 induced HCC metastasis.ResultsGain- and loss- of function analyses revealed that RPS7 promoted HCC cells adhesion, migration and invasion capabilities, as well as lung metastasis. Mechanistically, we uncovered that lysyl oxidase-like 2 (LOXL2) was a critical downstream target of RPS7. RPS7 could stabilize LOXL2 mRNA by binding to AUUUA motifs in the 3155-3375 region of the 3'UTR of LOXL2 mRNA, thus increased LOXL2 expression via elevating LOXL2 mRNA abundance. Further research revealed that LOXL2 could accelerate focal adhesion formation through maintaining the protein stability of ITGB1 and activating ITGB1-mediated FAK/SRC signaling pathway, and thereby contribute to the pro-metastasis effect of RPS7.ConclusionsTaken together, our data reveal a novel function of RPS7 in HCC metastasis, also reveal the critical roles of the RPS7/LOXL2/ITGB1 axis in HCC metastasis and shed new light on the exploration of molecular drugs against HCC."

基金机构：National Key Research and Development Program of China

基金资助正文：We would like to thank American Journal Experts (https://www.aje.cn/) for English language editing. We also thank Prof. Jie-Liang Chen from Fudan University for reviewing and revising.