MicroRNA-122 might be a double-edged sword in hepatocellular carcinomaписьмо
Аннотация: Tsai et al.1 reported that they used a high-throughput microRNA array to screen microRNAs associated with metastasis of hepatocellular carcinoma (HCC). They demonstrated that microRNA-122, a liver-specific microRNA, plays an important role in the regulation of intrahepatic metastasis of HCC by posttranscriptional down-regulation of a disintegrin and metallopeptidase 17. As microRNA has been regarded as the negative regulator of gene expression in, for example, cell differentiation, proliferation, migration, and invasion, microRNA-122–based therapeutics could be a promising strategy for clinical patients.1 However, this study has raised several confusing questions. First, Tsai et al.1 demonstrated that down-regulation of microRNA-122 is uniquely related to intrahepatic metastasis of HCC. However, a previous study demonstrated that microRNA-122 is down-regulated in both primary and metastatic HCC.2, 3 Here, the authors reported no obvious difference in microRNA-122 expression in normal adjacent tissues and T1 stage tumor tissues. This might be a contradictive result with respect to other published data. Second, because more than 85% of HCCs develop on account of infections with hepatitis B virus (HBV) or hepatitis C virus (HCV), chronic ethanol ingestion, or aflatoxin B1 exposure,4 besides providing the tumor-node-metastasis stage of the clinical patient, the authors should also list the aforementioned etiological parameters because HCV and HBV are important causes of HCC and the inhibition of virus replication is important to retard the process of carcinogenesis. Third, the most confusing question in this study arises from the authors' conclusion that a rational therapeutic strategy based on microRNA-122 may prove to be beneficial for patients with HCC. However, to the best of our knowledge, microRNA-122 also modulates HCV replication by binding to the 5′ noncoding region of HCV RNA, which is highly conserved in all six HCV genotypes. If microRNA-122 is ectopically expressed in patients with HCV infection to inhibit growth and metastasis of HCC, it can also stimulate the replication of HCV. Moreover, it has been demonstrated that HCV induces HCC by modulating the cytoskeleton, cell cycle, ubiquitin proteasome, and even immune response.5 Finally, we conclude that microRNA-122–based therapeutics might be a double-edged sword in the treatment of HCC. If such an approach is applied, the status of HCV infection in patients should be detected carefully. Rui Zhang* , Lei Wang* , Gui-Rong Yu* , Xiang Zhang* , Li-Bo Yao* , An-Gang Yang* , * State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an, China, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, China, Department of Immunology, Fourth Military Medical University, Xi'an, China.
Год издания: 2009
Авторы: Rui Zhang, Lei Wang, Gui-Rong Yu, Xiang Zhang, Libo Yao, Angang Yang
Издательство: Lippincott Williams & Wilkins
Источник: Hepatology
Ключевые слова: MicroRNA in disease regulation, Extracellular vesicles in disease, Circular RNAs in diseases
Другие ссылки: Hepatology (HTML)
PubMed (HTML)
PubMed (HTML)
Открытый доступ: closed
Том: 50
Выпуск: 4
Страницы: 1322–1323