Insulin-like Growth Factor regulates the lncRNA SNHG7 as part of a feedback loop that attenuates proliferation of breast cancer cells
Insulin-like growth factor 1 (IGF1) signaling is involved in the initiation and progression of a subset of breast cancers by inducing cell proliferation and survival. Although the signaling cascade following IGF1 receptor activation is well studied, the key elements of the robust transcriptional response governing IGF1’s actions are not well understood. ENCODE recently revealed that the majority of the genome is transcribed and that there are more long non-coding RNAs (lncRNAs) than protein coding genes. Several of these are dysegulated in human cancer. However, the studies to determine the mechanisms of how these lncRNAs are regulated and function are in their infancy. Here we show that IGF1 stimulation of a breast cancer cell line causes significant changes in the expressions of a subset of putative lncRNAs. SNHG7, a member of the small nucleolar host gene family, is a highly expressed lncRNA that is consistently and significantly down regulated by IGF1 signaling. We demonstrate that IGF1 signaling decreases SNHG7 expression by a post-transcriptional mechanism through the MAPK pathway. We further demonstrate that SNHG7 regulates proliferation of breast cancer cell lines in a dose-dependent manner. We observed that silencing SNHG7 expression stimulates cell cycle arrest in G0/G1 by altering the expression of many of the same genes as IGF1 signaling and by directly regulating the expression of a significant proportion of IGF1 signaling molecules. Finally, we show with TCGA data that SNHG7 is overexpressed in the tumors of a subset of breast cancer patients and that these patients have lower overall survival than patients without elevated SNHG7 expression. Therefore, we propose that SNHG7 is a putative lncRNA oncogene that is controlled by growth factor signaling in a feedback mechanism to prevent hyperproliferation, and that this regulation can be lost in the development or progression of breast cancer.