Silencing LINC01547 induces hepatocellular carcinoma cell apoptosis and metastasis inhibition via the ADAR1/FAK and miR-146b-5p/RAC1 axes

被引:0
作者
Wang, Dan [1 ]
Zhao, Huijie [2 ]
Zhao, Ying [2 ]
An, Xuejing [2 ]
Shi, Chuanqin [3 ]
Pan, Zhaohai [2 ]
Zheng, Qiusheng [2 ]
Wang, Xin [1 ,4 ,5 ]
Lu, Jun [6 ]
Li, Defang [2 ,7 ]
机构
[1] Ocean Univ China, Sch Med & Pharm, Key Lab Marine Drugs, Minist Educ, Qingdao 266003, Peoples R China
[2] Binzhou Med Univ, Sch Tradit Chinese Med, Featured Lab Biosynth & Target Discovery Act Compo, Yantai 264003, Shandong, Peoples R China
[3] Binzhou Med Univ, Ctr Translat Med, Zibo Cent Hosp, Zibo 255020, Peoples R China
[4] Hainan Univ, Key Lab Trop Biol Resources, Minist Educ, Haikou 570228, Peoples R China
[5] Hainan Univ, Hlth Inst 1, Sch Pharmaceut Sci, Haikou 570228, Peoples R China
[6] Chengdu Univ Tradit Chinese Med, Sch Pharm, State Key Lab Southwestern Chinese Med Resources, Chengdu 611137, Peoples R China
[7] Hebei Univ Chinese Med, Coll Pharm, Shijiazhuang 050200, Peoples R China
基金
中国国家自然科学基金;
关键词
Hepatocellular carcinoma; LINC01547; ADAR1/FAK; miR-146b-5p/RAC1; Apoptosis; Metastasis; LONG NONCODING RNAS; LNCRNA; BUFOTALIN; INVASION;
D O I
10.1007/s10495-024-02070-0
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Growing research indicates that long noncoding RNAs (lncRNAs) are pivotal in the development and advancement of hepatocellular carcinoma (HCC). Our research pinpointed LINC01547 as a notable lncRNA that was significantly downregulated in Hep3B cells treated with bufotalin, whereas it exhibited elevated expression levels in HCC tumor tissues. Further study found that silencing LINC01547 markedly suppressed proliferation, induced apoptosis, and inhibited migration and invasion in Hep3B and HepG2 cells. LINC01547 knockdown reduced ADAR1 expression, which led to apoptosis and suppressed metastasis via inhibition of the FAK signaling pathway. Additionally, silencing LINC01547 upregulated miR-146b-5p, which in turn decreased RAC1 levels, further promoting apoptosis and inhibiting metastasis in HCC cells. In vivo, a Hep3B tumor-bearing mouse model confirmed the antitumor effects of LINC01547 silencing. Our findings demonstrate that LINC01547 regulates HCC cell apoptosis and metastasis through the ADAR1/FAK and miR-146b-5p/RAC1 pathways, suggesting that LINC01547 may serve as a biomarker and potential therapeutic target for HCC.
引用
收藏
页码:936 / 954
页数:19
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