In Cancer Research this week, researchers in China write that genetic variation in an miRNA-1827 binding site in the MYCL1 gene alters susceptibility to lung cancer. The researchers took an in silico approach to identifying SNPs within the 3′ UTR of miRNA genes that are deregulated in human small-cell lung cancer, and then looked at the possible associations between those SNPs and lung cancer susceptibility in 666 patients and 758 controls. "We identified 2 SNPs, rs3134615 and rs2291854, which were located in the 3′-UTR of the L-MYC gene MYCL1 and the neuronal development Achaete-Scute Complex homolog ASCL1. Case-control analyses showed that the rs3134615T allele was associated with a significantly increased risk of small-cell lung cancer," the authors write. "Our findings define a 3′-UTR SNP in the human L-MYC oncogene that may increase susceptibility to small-cell lung cancer, possibly resulting from attenuated interaction with the miRNA hsa-miR-1827."
Also in Cancer Research this week, researchers in the US and Taiwan say BMP4 promotes the growth of prostate cancer cells in bone through osteogenesis. The team subcutaneously implanted two xenografts, MDA-PCa-118b and MDA-PCa-133, generated from prostate cancer bone metastases into severe combined immunodeficient mice, and found that MDA-PCa-118b induced strong ectopic bone formation. "We found that the osteogenic MDA-PCa-118b xenograft expressed higher levels of bone morphogenetic protein BMP4 and several cytokines including interleukin-8, growth-related protein, and CCL2," the authors write. "We showed that BMP4 secreted from MDA-PCa-118b contributed to about a third of the osteogenic differentiation seen in MDA-PCa-118b tumors."
Finally, researchers in Germany say that microRNA replacement therapy for miR-145 and miR-33a proved efficacious in a model of colon carcinoma. MiR-145 is down-regulated in various cancers, including colon cancer, the authors write, and miR-33a down-regulates the oncogenic kinase Pim-1. In this study, the team reports delivering miRNA using a polyethylenimine-mediated delivery of unmodified miRNAs. "After systemic or local application of low molecular weight PEI/miRNA complexes, intact miRNA molecules were delivered into mouse xenograft tumors, where they caused profound antitumor effects," the researchers write. "MiR-145 delivery reduced tumor proliferation and increased apoptosis, with concomitant repression of c-Myc and ERK5 as novel regulatory target of miR-145. Similarly, systemic injection of PEI-complexed miR-33a was validated as a novel therapeutic targeting method for Pim-1, with antitumor effects comparable with PEI/siRNA-mediated direct in vivo knockdown of Pim-1 in the model."