RNA-binding protein CCDC137 activates AKT signaling and promotes hepatocellular carcinoma through a novel non-canonical role of DGCR8 in mRNA localization.
RNA-binding protein CCDC137 activates AKT signaling and promotes hepatocellular carcinoma through a novel non-canonical role of DGCR8 in mRNA localization.
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DOI：
10.1186/s13046-023-02749-3
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发表时间：
2023-08-05
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RNA binding proteins (RBPs)—regulated gene expression play a vital role in various pathological processes, including the progression of cancer. However, the role of RBP in hepatocellular carcinoma (HCC) remains much unknown. In this study, we aimed to explore the contribution of RBP CCDC137 in HCC development. We analyzed the altered expression level and clinical significance of CCDC137 in database and HCC specimens. In vitro cell assays and in vivo spontaneous mouse models were used to assess the function of CCDC137. Finally, the molecular mechanisms of how CCDC137 regulates gene expression and promotes HCC was explored. CCDC137 is aberrantly upregulated in HCC and correlates with poor clinical outcomes in HCC patients. CCDC137 markedly promoted HCC proliferation and progression in vitro and in vivo. Mechanistically, CCDC137 binds with FOXM1, JTV1, LASP1 and FLOT2 mRNAs, which was revealed by APOBEC1-mediated profiling, to increase their cytoplasmic localization and thus enhance their protein expressions. Upregulation of FOXM1, JTV1, LASP1 and FLOT2 subsequently synergistically activate AKT signaling and promote HCC. Interestingly, we found that CCDC137 binds with the microprocessor protein DGCR8 and DGCR8 has a novel non-canonical function in mRNA subcellular localization, which mediates the cytoplasmic distribution of mRNAs regulated by CCDC137. Our results identify a critical proliferation-related role of CCDC137 and reveal a novel CCDC137/DGCR8/mRNA localization/AKT axis in HCC progression, which provide a potential target for HCC therapy. The online version contains supplementary material available at 10.1186/s13046-023-02749-3.
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影响因子：
16.6
作者：
Hang Q;Zeng L;Wang L;Nie L;Yao F;Teng H;Deng Y;Yap S;Sun Y;Frank SJ;Chen J;Ma L
通讯作者：
Ma L
ECHS1 是 LASP1 的相互作用蛋白，通过调节神经酰胺糖基化诱导鞘脂代谢失衡，促进结直肠癌进展
影响因子：
9
作者：
Li R;Hao Y;Wang Q;Meng Y;Wu K;Liu C;Xu L;Liu Z;Zhao L
通讯作者：
Zhao L
DOI：
10.1002/advs.202301983
发表时间：
2023-08
期刊：
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
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--
作者：
通讯作者：
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影响因子：
14.9
作者：
Mestre-Farras, Neus;Guerrero, Santiago;Bley, Nadine;Rivero, Ezequiel;Coll, Olga;Borras, Eva;Sabido, Eduard;Indacochea, Alberto;Casillas-Serra, Carlos;Jarvelin, Aino, I;Oliva, Baldomero;Castello, Alfredo;Huettelmaier, Stefan;Gebauer, Fatima
通讯作者：
Gebauer, Fatima
影响因子：
48
作者：
Meyer, Kate D.
通讯作者：
Meyer, Kate D.