RALYL increases hepatocellular carcinoma stemness by sustaining the mRNA stability of TGF-β2.
RALYL increases hepatocellular carcinoma stemness by sustaining the mRNA stability of TGF-β2.
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RALYL 通过维持 TGF-β 2 mRNA 稳定性来增加肝细胞癌干性
DOI：
10.1038/s41467-021-21828-7
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发表时间：
2021-03-09
影响因子：
16.6
通讯作者：
Guan XY
中科院分区：
文献类型：
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作者：
Wang X;Wang J;Tsui YM;Shi C;Wang Y;Zhang X;Yan Q;Chen M;Jiang C;Yuan YF;Wong CM;Liu M;Feng ZY;Chen H;Ng IOL;Jiang L;Guan XY
越来越多的证据表明，癌症干细胞表现出许多与其祖先祖细胞相似的分子特征和表型。在本研究中，人胚胎干细胞被诱导沿着肝谱系分化为肝细胞，以模拟体外肝脏的发育。鉴定出肝祖细胞特异性基因 RALY RNA 结合蛋白样 (RALYL)。 RALYL表达与临床HCC患者的不良预后、分化不良和转移相关。功能研究表明，RALYL 可以促进 HCC 致瘤性、自我更新、化疗耐药性和转移。此外，分子机制研究表明，RALYL 可以通过减少 N6-甲基腺苷 (m6A) 修饰来上调 TGF-β2 mRNA 稳定性。 TGF-β 信号传导以及随后的 PI3K/AKT 和 STAT3 通路（由 RALYL 上调）有助于增强 HCC 干细胞性。总的来说，RALYL 是一种肝祖细胞特异性基因，通过维持 TGF-β2 mRNA 的稳定性来调节 HCC 干性。这些发现可能会激发 HCC 的精确治疗策略。 RALYL 是一种肝祖细胞特异性基因，但其在肝细胞癌 (HCC) 中的作用仍不清楚。在此，作者证明 RALYL 通过减少 N6-甲基腺苷修饰上调 TGF-β2 mRNA 稳定性来调节 HCC 干性。
Growing evidences suggest that cancer stem cells exhibit many molecular characteristics and phenotypes similar to their ancestral progenitor cells. In the present study, human embryonic stem cells are induced to differentiate into hepatocytes along hepatic lineages to mimic liver development in vitro. A liver progenitor specific gene, RALY RNA binding protein like (RALYL), is identified. RALYL expression is associated with poor prognosis, poor differentiation, and metastasis in clinical HCC patients. Functional studies reveal that RALYL could promote HCC tumorigenicity, self-renewal, chemoresistance, and metastasis. Moreover, molecular mechanism studies show that RALYL could upregulate TGF-β2 mRNA stability by decreasing N6-methyladenosine (m6A) modification. TGF-β signaling and the subsequent PI3K/AKT and STAT3 pathways, upregulated by RALYL, contribute to the enhancement of HCC stemness. Collectively, RALYL is a liver progenitor specific gene and regulates HCC stemness by sustaining TGF-β2 mRNA stability. These findings may inspire precise therapeutic strategies for HCC. RALYL is a liver progenitor cell-specific gene but its role in hepatocellular carcinoma (HCC) remains unknown. Here, the authors demonstrate that RALYL regulates HCC stemness through upregulation of TGF-β2 mRNA stability by decreasing N6-methyladenosine modification.
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影响因子：
64.5
作者：
Kim J;Woo AJ;Chu J;Snow JW;Fujiwara Y;Kim CG;Cantor AB;Orkin SH
通讯作者：
Orkin SH
影响因子：
7.3
作者：
Busch, Anke;Hertel, Klemens J.
通讯作者：
Hertel, Klemens J.
影响因子：
13.5
作者：
Mishra, Lopa;Banker, Tanuj;Murray, Joseph;Byers, Stephen;Thenappan, Arun;He, Aiwu Ruth;Shetty, Kirti;Johnson, Lynt;Reddy, E. P.
通讯作者：
Reddy, E. P.
影响因子：
50.3
作者：
Li Z;Weng H;Su R;Weng X;Zuo Z;Li C;Huang H;Nachtergaele S;Dong L;Hu C;Qin X;Tang L;Wang Y;Hong GM;Huang H;Wang X;Chen P;Gurbuxani S;Arnovitz S;Li Y;Li S;Strong J;Neilly MB;Larson RA;Jiang X;Zhang P;Jin J;He C;Chen J
通讯作者：
Chen J
TGFβ 信号的背景
DOI：
10.1038/nrm3434
发表时间：
2012-10
期刊：
Nature reviews. Molecular cell biology
影响因子：
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作者：
通讯作者：
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