McDaniel Kelly, Hall Chad, Sato Keisaku, Lairmore Terry, Marzioni Marco, Glaser Shannon, Meng Fanyin, Alpini Gianfranco
Research, Central Texas Veterans Health Care System, Temple, Texas; Baylor Scott & White Digestive Disease Research Center, Scott & White Memorial Hospital, Temple, Texas; Operational Funds, Baylor Scott & White, Temple, Texas; Department of Medicine, Baylor Scott & White and Texas A & M Health Science Center, Temple, Texas;
Operational Funds, Baylor Scott & White, Temple, Texas; Department of Surgery, Baylor Scott & White and Texas A & M Health Science Center, Temple, Texas; and.
Am J Physiol Gastrointest Liver Physiol. 2016 May 15;310(10):G757-65. doi: 10.1152/ajpgi.00080.2016. Epub 2016 Mar 24.
The diagnosis and treatment of liver disease remain a major health concern worldwide because of the diverse etiologies of this disease. For this reason, new therapeutic targets are greatly needed to halt the progression of this damaging disease. Upon initiation of liver injury by viral infection, autoimmune disease or toxin, and/or hepatitis, chronic disease may develop, which can progress to cirrhosis, hepatocellular carcinoma (HCC), cholangiocarcinoma, liver failure, or death. The Lin28/lethal-7 (let-7) molecular switch has emerged as a central regulator of multiorgan injuries and cancer development. Lin28 is a stem cell marker vital to initiation or maintenance of a stem cell phenotype. Lin28 has not been extensively studied in the liver, despite its ability to induce tissue regeneration via reprogramming of oxidative enzymes in other tissues and its involvement with numerous upstream regulators and downstream targets in liver disease. Theoretically, overexpression of Lin28 in certain forms of liver disease could be a potential treatment that aids in liver regeneration. Alternatively, Lin28 has been implicated numerous times in the progression of diverse cancer types and is associated with increased severity of disease. In this case, Lin28 could be a potential inhibitory target to prevent malignant transformation in the liver. This review seeks to characterize the role of Lin28 in liver disease.
由于肝脏疾病病因多样，其诊断和治疗仍是全球主要的健康问题。因此，迫切需要新的治疗靶点来阻止这种破坏性疾病的进展。在病毒感染、自身免疫性疾病、毒素和/或肝炎引发肝损伤后，可能会发展为慢性病，进而进展为肝硬化、肝细胞癌（HCC）、胆管癌、肝衰竭或死亡。Lin28/致死-7（let-7）分子开关已成为多器官损伤和癌症发展的核心调节因子。Lin28是一种对干细胞表型的启动或维持至关重要的干细胞标志物。尽管Lin28能够通过重编程其他组织中的氧化酶诱导组织再生，并且在肝脏疾病中涉及众多上游调节因子和下游靶点，但它在肝脏中的研究并不广泛。从理论上讲，在某些形式的肝脏疾病中过表达Lin28可能是一种有助于肝脏再生的潜在治疗方法。另外，Lin28多次与多种癌症类型的进展有关，并与疾病严重程度增加相关。在这种情况下，Lin28可能是预防肝脏恶性转化的潜在抑制靶点。本综述旨在阐述Lin28在肝脏疾病中的作用。
