文献类型：期刊文献

英文题名：MicroRNA 96 Is a Post-Transcriptional Suppressor of Anaplastic Lymphoma Kinase Expression

作者：Vishwamitra, Deeksha[4];Li, Yong;Wilson, Desiree;Manshouri, Roxsan;Curry, Choladda V.[5];Shi, Bin;Tang, Xi Ming[2];Sheehan, Andrea M.[5];Wistuba, Ignacio I.[2,3];Shi, Ping[6];Amin, Hesham M.[1,4]

机构：[1]Univ Texas MD Anderson Canc Ctr, Unit 72, Dept Hematopathol, Houston, TX 77030 USA;[2]Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA;[3]Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA;[4]Univ Texas Grad Sch Biomed Sci, Houston, TX USA;[5]Texas Childrens Hosp, Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA;[6]E China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

年份：2012

卷号：180

期号：5

起止页码：1772

外文期刊名：AMERICAN JOURNAL OF PATHOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000303641000003)】；

基金：Supported by grants from the National Cancer Institute (K08CA114395 and R01CA151533), the Physician Scientist Program Award, and a Bridge Funding Grant from The University of Texas MD Anderson Cancer Center (H.M.A.).

语种：英文

摘要：Anaplastic lymphoma kinase (ALK) constitutes a part of the oncogenic fusion proteins nucleophosmin-ALK and echinoderm microtubule-associated protein like 4-ALK, which are aberrantly expressed in a subset of T-cell anaplastic large-cell lymphoma and non-small-cell lung cancer, respectively. The expression of mutated, constitutively active ALK also occurs in a subset of neuroblastoma tumors. ALK is believed to play an important role in promoting tumor survival. Nevertheless, the mechanisms underlying the expression of ALK in cancer cells are not completely known. MicroRNA (miR) has been implicated in the regulation of the expression of both oncogenes and tumor suppressor genes. We tested the hypothesis that the expression of ALK could be regulated by miR. Three Internet-based algorithms identified miR-96 to potentially bind with the ALK 3'-untranslated region. Notably, miR-96 levels were markedly decreased in ALK-expressing cancer cell lines and primary human tumors compared with their normal cellular and tissue counterparts. Transfection of the cell lines with miR-96 decreased levels of the different forms of ALK protein, without significant effects on ALK mRNA. Furthermore, miR-96 decreased the phosphorylation of ALK target proteins, including Akt, STAT3, JNK, and type I insulin-like growth factor receptor, and it down-regulated JunB. These effects were associated with reduced proliferation, colony formation, and migration of ALK-expressing cancer cells. These data provide novel evidence that decreases in miR-96 could represent a mechanism underlying the aberrant expression of ALK in cancer cells. (Am J Pathol 2012, 180:1772-1780; DOI: 10.1016/j.ajpath.2012.01.008)