Microarray analysis and qRT-PCR also demonstrate that miR-135b levels are more than twofold higher in head and neck squamous cell carcinoma (HNSCC) in an orthotopic mouse model compared to controls ( 6). Clinically, deregulation of this pathway also appears to be an important driver of hepatocellular and cholangiocarcinoma, although, to our knowledge, its regulation has not been linked to miR-135b in the setting of liver disease ( 5). Downregulation of LATS2 and LZTS1 and consequent nuclear localization of the transcriptional activator TAZ in patients with high miR-135b levels correlated with poor overall survival ( 4). Mammalian orthologs within the Hippo pathways include LATS2 and LZTS1, which were identified as targets of miR-135b. The investigators demonstrated that miR-135b suppresses key components of the Hippo pathway, a serine-threonine kinase pathway studied extensively in Drosophila melanogaster that plays a role in inhibition of overgrowth, regulation of cell division, and apoptosis. ![]() In vivo, stable expression of a miR-135b antagonist decreased the number of metastatic tumor nodules in mice injected with highly invasive CL1-5-F4 cells shown to have high levels of miR-135b ( 4).Ĭlinically, high levels of miR-135b in lung cancer specimens significantly correlated with decreased overall survival ( 4). Overexpression of miR-135b conferred an increased tumorigenic ability to the relatively benign CL1-0 cells, resulting in more than a fourfold greater tumor burden in xenograft mouse models. Microarray analysis and quantitative reverse transcription-PCR (qRT-PCR) studies in NSCLC have demonstrated that miR-135b upregulation is far more robust in highly invasive lines compared to the less invasive. MiR-135b levels are elevated in a variety of cancers including breast, non-small cell lung cancer (NSCLC), prostate, and colon ( 1– 3). MicroRNA-135b (miR-135b) Overexpression and Oncogenic Behavior ![]() In this discussion, we review the literature on miR-135b, purporting its role as an oncogene in multiple cancers, and we highlight STAT3 inhibition as a potential therapeutic strategy mediated by miR-135b and demonstrate particular clinical relevance to colon cancer. ![]() MicroRNAs, which encompass over 1000 short, endogenous nucleic acids, include important candidates that drive carcinogenesis. The study of regulatory non-coding RNAs has deepened our understanding of cancer on the molecular and clinical front.
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