Elevated FAM134B expression induces radiation-sensitive in hepatocellular carcinoma.
Elevated FAM134B expression induces radiation-sensitive in hepatocellular carcinoma.
复制标题
DOI：
10.1186/s12885-023-11030-x
复制
发表时间：
2023-07-17
期刊：
影响因子：
3.8
通讯作者：
Li, Heping
中科院分区：
文献类型：
--
作者：
Xie, Binhui;Xie, Yuankang;Fang, Cuifu;Zhong, Baiyin;Ye, Rong;Zhang, Jianhong;Liu, Qingquan;Li, Heping
已有研究表明，具有序列相似性的家族成员134成员B(FAM134B)参与了肿瘤的发生发展，但FAM134B在肝细胞癌放射治疗耐药中的作用及其分子机制尚不清楚。因此，阐明肝癌放射治疗耐药的分子机制，寻找新的生物标志物可能是临床有效的治疗手段。实时定量聚合酶链式反应检测FAM134B的蛋白表达，Western印迹法检测FAM134B的mRNA表达。采用免疫组织化学方法检测132例肝细胞癌组织中FAM134B的表达与临床病理特征的关系。采用原位模型、结肠形成、流式细胞术和TUNEL法等功能检测方法，研究FAM134B在人肝细胞癌进展中的致癌作用。此外，利用免疫印迹和荧光素酶活性分析，进一步探讨了FAM134B促进肝癌细胞放射增敏的机制。我们注意到FAM134B在肝细胞癌中表达下调，这与肝细胞癌患者的放射抵抗有关。FAM134B的过表达有助于肝癌细胞对辐射的敏感性；然而，抑制FAM134B使肝癌细胞株在体外和体内都具有辐射抗性。此外，我们还发现FAM134B与FMS相关受体酪氨酸激酶3(Flt3)相互作用，下调FAM134B激活的JAK/STAT3信号通路。重要的是，对JAK/STAT3信号通路的药理抑制显著抵消了FAM134B诱导的肝癌放射抗性的下调和放射治疗效果的增强。我们的研究结果表明，FAM134B可能是治疗放疗耐受的肝癌患者的一个潜在的治疗生物标志物。网上版载有补充材料，可在10.1186/s12885-023-11030-x查阅。
Previous studies have shown that Family with sequence similarity 134 member B (FAM134B) was involved in the occurrence and development of malignancy, however, the function and molecular mechanism of FAM134B in Hepatocellular Carcinoma (HCC) radiotherapy resistance remain unclear. Therefore, it may clinical effective to clarify the molecular mechanism and identify novel biomarker to overcome radiotherapy resistance in HCC. The protein and mRNA expression of FAM134B were determined using Real-time PCR and Western blot, respectively. IHC assay was performed to investigate the association between FAM134B expression and the clinicopathological characteristics of 132 HCC patients. Functional assays, such as in situ model, colon formation, FACS, and Tunel assay were used to determine the oncogenic role of FAM134B in human HCC progression. Furthermore, western blotting and luciferase assay were used to determine the mechanism of FAM134B promotes radiation-sensitive in HCC cells. We noted that FAM134B was downregulated in HCC, which was correlated with the radiation resistance in patients with HCC. Overexpression of FAM134B contribute to radiation sensitive in HCC; however, inhibition of FAM134B confers HCC cell lines to radiation resistance both in vitro and in vivo. Moreover, we found that FAM134B interacts with FMS related receptor tyrosine kinase 3 (FLT3) and downregulation of FAM134B activated JAK/Stat3 signaling pathway. Importantly, pharmacological inhibition of JAK/Stat3 signaling pathway significantly counteracted downregulation of FAM134B-induced radiation resistance and enhanced radiation therapeutic efficacy in HCC. Our findings suggest that FAM134B may be a potential therapeutic biomarker for the treatment of HCC patients with radiotherapy tolerance. The online version contains supplementary material available at 10.1186/s12885-023-11030-x.
登录
查看更多内容
影响因子：
2.9
作者：
Davila JA;Duan Z;McGlynn KA;El-Serag HB
通讯作者：
El-Serag HB
miR-101 通过靶向 stathmin 1 使人鼻咽癌细胞对辐射敏感。
影响因子：
3.4
作者：
Sun Q;Liu T;Zhang T;Du S;Xie GX;Lin X;Chen L;Yuan Y
通讯作者：
Yuan Y
影响因子：
--
作者：
Ghouri YA;Mian I;Rowe JH
通讯作者：
Rowe JH
影响因子：
11.2
作者：
Hussain, S. Farzana;Kong, Ling-Yuan;Heimberger, Amy B.
通讯作者：
Heimberger, Amy B.
影响因子：
2.6
作者：
Forman, Oliver P.;Hitti, Rebekkah J.;Mellersh, Cathryn
通讯作者：
Mellersh, Cathryn