Long non-coding RNAs (lncRNAs) represent an emerging layer of cancer biology, contributing to tumor proliferation, invasion, and metastasis. Here, we describe a role for the oncogenic lncRNA PCAT-1 in prostate cancer proliferation through cMyc. We find that PCAT-1-mediated proliferation is dependent on cMyc protein stabilization, and using expression profiling, we observed that cMyc is required for a subset of PCAT-1-induced expression changes. The PCAT-1-cMyc relationship is mediated through the post-transcriptional activity of the MYC 3' untranslated region, and we characterize a role for PCAT-1 in the disruption of MYC-targeting microRNAs. To further elucidate a role for post-transcriptional regulation, we demonstrate that targeting PCAT-1 with miR-3667-3p, which does not target MYC, is able to reverse the stabilization of cMyc by PCAT-1. This work establishes a basis for the oncogenic role of PCAT-1 in cancer cell proliferation and is the first study to implicate lncRNAs in the regulation of cMyc in prostate cancer.
Recommended CitationPrensner, John R.; Chen, Wei; Han, Sumin; Iyer, Matthew K.; Cao, Qi; Kothari, Vishal; Evans, Joseph R.; Knudsen, Karen E.; Paulsen, Michelle T.; Ljungman, Mats; Lawrence, Theodore S.; Chinnaiyan, Arul M.; and Feng, Felix Y., "The long non-coding RNA PCAT-1 promotes prostate cancer cell proliferation through cMyc." (2014). Department of Cancer Biology Faculty Papers. Paper 100.
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