Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06511, USA.
Proc Natl Acad Sci U S A. 2012 Jun 26;109(26):E1695-704. doi: 10.1073/pnas.1201516109. Epub 2012 Jun 8.
MicroRNA-155 (miR-155) is an oncogenic microRNA that regulates several pathways involved in cell division and immunoregulation. It is overexpressed in numerous cancers, is often correlated with poor prognosis, and is thus a key target for future therapies. In this work we show that overexpression of miR-155 in lymphoid tissues results in disseminated lymphoma characterized by a clonal, transplantable pre-B-cell population of neoplastic lymphocytes. Withdrawal of miR-155 in mice with established disease results in rapid regression of lymphadenopathy, in part because of apoptosis of the malignant lymphocytes, demonstrating that these tumors are dependent on miR-155 expression. We show that systemic delivery of antisense peptide nucleic acids encapsulated in unique polymer nanoparticles inhibits miR-155 and slows the growth of these "addicted" pre-B-cell tumors in vivo, suggesting a promising therapeutic option for lymphoma/leukemia.
MicroRNA-155 (miR-155) 是一种致癌 microRNA，调节细胞分裂和免疫调节涉及的几个途径。它在许多癌症中过度表达，通常与预后不良相关，因此是未来治疗的关键靶点。在这项工作中，我们表明 miR-155 在淋巴组织中的过表达导致弥漫性淋巴瘤，其特征是具有克隆性、可移植性的前 B 细胞肿瘤淋巴细胞群。在已建立疾病的小鼠中撤回 miR-155 导致淋巴结病的快速消退，部分原因是恶性淋巴细胞的凋亡，表明这些肿瘤依赖于 miR-155 的表达。我们表明，封装在独特聚合物纳米粒子中的反义肽核酸的系统递送抑制 miR-155 并减缓这些“成瘾”前 B 细胞肿瘤在体内的生长，这为淋巴瘤/白血病提供了一种有前途的治疗选择。
