Macrophage polarization-associated lnc-Ma301 interacts with caprin-1 to inhibit hepatocellular carcinoma metastasis through the Akt/Erk1 pathway

Cancer Cell International

Chao Ou¹  Jian-Hong Zhong²  Tao Bai²  Jie Chen²  Hong-Lin Luo²  Tao Luo²  Fei-Xiang Wu²  Le-Qun Li²  Jun-Jie Liu³ 

[1]Department of Clinical Laboratory Medicine, Guangxi Medical University Cancer Hospital

[2]Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital

[3]Department of Ultrasound, Guangxi Medical University Cancer Hospital

关键词: Hepatocellular carcinoma;    Long non-coding RNAs;    Cancer migration;    Epithelial–mesenchymal transition;    Metastasis;   

DOI  :  10.1186/s12935-021-02133-1

来源: DOAJ

【 摘 要 】

Abstract Background Epithelial–mesenchymal transition (EMT) promotes migration, invasion, and metastasis of hepatocellular carcinoma (HCC) cells. The molecular mechanisms behind EMT and metastasis in HCC remain unclear. Methods Microarray analysis was used to identify lncRNAs expression during polarization of U937 macrophages from M2 to M1 phenotype. The expression of the identified lncRNA was compared between clinical samples of HCC tissues or adjacent normal tissues, as well as between HCC and normal liver cell lines. lnc-Ma301 was overexpressed or knocked-down in HCC cell lines, and the effects were assessed in vitro and in vivo. Interactions among lnc-Ma301 and its potential downstream targets caprin-1 were investigated in HCC cell lines. Effects of lnc-Ma301 over- and underexpression on the Akt/Erk1 signaling pathways were examined. Results Microarray analyses identified lnc-Ma301 as one of the most overexpressed long non-coding RNAs during polarization of U937 macrophages from M2 to M1 phenotype. Lnc-Ma301 showed lower expression in HCC tissues than in adjacent normal tissues, and lower expression was associated with worse prognosis. Activation of lnc-Ma301 inhibited cell proliferation, migration and EMT in HCC cell cultures, and it inhibited lung metastasis of HCC tumors in mice. Mechanistic studies suggested that lnc-Ma301 interacts with caprin-1 to inhibit HCC metastasis and EMT through Akt/Erk1 pathway. Conclusions Lnc-Ma301 may help regulate onset and metastasis of HCC.

【 授权许可】

Unknown