Department of Laboratory Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
Department of Laboratory Medicine, Chongqing Traditional Chinese Medicine Hospital, Chongqing 400021, China.
Dis Markers. 2020 Oct 8;2020:2032056. doi: 10.1155/2020/2032056. eCollection 2020.
Substantial advance supports that CMTM2 serve as an important performer in physiological and pathological processes. However, very little is clear about the relationship between CMTM2 and HBV-related disorders. Here, for the first time, we explore that whether or not serum CMTM2 is involved in HBV-related diseases. We found that CMTM2 values were significantly lower in patients compared to healthy control (p <0.001), using ELISA assay. Furthermore, serum CMTM2 levels were negatively correlated with HBV DNA levels in CHB patients but not correlated with the serum levels of ALT and AST. Serum CMTM2 concentrations were not correlated with the serum levels of ALT, AST and HBV DNA load in HBLC and HCC patients. In addition, analysis of the ROC curve indicated that CMTM2 levels were significantly associated with the diagnostic value of HBV-related disorders. Finally, downregulation of CMTM2 was observed in HBV-infected cell model. CMTM2 degradation could be attributed to HBx-activated Lys48 (K48)-linked polyubiquitination, which was abolished by treatment with the proteasome inhibitor MG132. HBV infection suppresses CMTM2 expression by activating ubiquitin-proteasome system. Serum CMTM2 levels can be adopted as an effective indicator of the pathogenesis of HBV-related disorders.
大量研究支持 CMTM2 在生理和病理过程中发挥重要作用。然而,CMTM2 与 HBV 相关疾病的关系仍不清楚。在这里,我们首次探讨了血清 CMTM2 是否参与 HBV 相关疾病。我们发现,与健康对照组相比,患者的 CMTM2 值显著降低(p<0.001),采用 ELISA 法检测。此外,在 CHB 患者中,血清 CMTM2 水平与 HBV DNA 水平呈负相关,但与 ALT 和 AST 血清水平无关。在 HBLC 和 HCC 患者中,血清 CMTM2 浓度与 ALT、AST 和 HBV DNA 载量的血清水平无关。此外,ROC 曲线分析表明,CMTM2 水平与 HBV 相关疾病的诊断价值显著相关。最后,在 HBV 感染的细胞模型中观察到 CMTM2 的下调。CMTM2 的降解归因于 HBx 激活的 Lys48(K48)连接的多泛素化,用蛋白酶体抑制剂 MG132 处理可消除这种多泛素化。HBV 感染通过激活泛素-蛋白酶体系统抑制 CMTM2 的表达。血清 CMTM2 水平可作为 HBV 相关疾病发病机制的有效指标。