The contribution of mitochondrial dynamics to the development and progression of hepatocellular carcinoma (HCC) remains controversial. Accordingly, the present study tries to illustrate the role of mitochondrial dynamics proteins (mitofusin-2 (Mfn2) and YME1L) in hepatocarcinogenesis. Five groups were used: the control group and three HCC groups (after 8, 16, and 24 weeks from DENA induction). The last group was treated with Sorafenib (SP) (10 mg/kg), via oral gavage for 4 weeks after cancer induction. This study revealed that Mfn-2 was downregulated and YME1l was overexpressed in different HCC groups. This dysregulation of mitochondrial dynamics proteins was associated with high hepatic levels of cyclin D1, MMP-9, and MDA and overexpression of ki67 as well as decreasing the hepatic expression of tissue inhibitor of matrix metalloproteinase-3 (Timp-3) and Bax. To confirm the possible role of Mfn2 and YME1L in HCC, we assessed the effect of sorafenib on these parameters and its related HCC characteristics. Sorafenib corrected the level of Mfn2 and YME1L and decreased tumor cell proliferation as well. We also elucidated that mitochondrial dynamics proteins (Mfn2 and YME1L) could be a good therapeutic target for HCC.

中文翻译：

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评估 YME1L 和 mitofusin2 作为肝细胞癌可能的诊断和/或治疗靶点

线粒体动力学对肝细胞癌 (HCC) 的发展和进展的贡献仍然存在争议。因此，本研究试图阐明线粒体动力学蛋白（mitofusin-2 (Mfn2) 和 YME1L）在肝癌发生中的作用。使用了五个组：对照组和三个 HCC 组（在 DENA 诱导后 8、16 和 24 周后）。最后一组在癌症诱导后通过口服强饲法接受索拉非尼 (SP) (10 mg/kg) 治疗 4 周。这项研究表明，Mfn-2 在不同的 HCC 组中被下调，YME1l 被过度表达。线粒体动力学蛋白的这种失调与细胞周期蛋白 D1、MMP-9、和 MDA 以及 ki67 的过表达以及降低基质金属蛋白酶 3 (Timp-3) 和 Bax 组织抑制剂的肝脏表达。为了确认 Mfn2 和 YME1L 在 HCC 中的可能作用，我们评估了索拉非尼对这些参数及其相关 HCC 特征的影响。索拉非尼纠正了 Mfn2 和 YME1L 的水平，并减少了肿瘤细胞增殖。我们还阐明了线粒体动力学蛋白（Mfn2 和 YME1L）可能是 HCC 的良好治疗靶点。