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MicroRNAs associated with the mir‐17‐92 cluster are crucial regulators of the mammalian cell cycle, as they inhibit transcription factors related to the E2F family that tightly control decision‐making events for a cell to commit for active cellular proliferation. Intriguingly, in many solid cancers, these mir‐17‐92 cluster members are overexpressed, whereas in some hematopoietic cancers they are down‐regulated. Our proposed model of the Myc/E2F/mir‐17‐92 network demonstrates that the differential expression pattern of mir‐17‐92 in different cell types can be conceived due to having a contrasting E2F dynamics induced by mir‐17‐92. The model predicts that by explicitly altering the mir‐17‐92‐related part of the network, experimentally it is possible to control cellular proliferation in a cell type‐dependent manner for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Highlights: [•] miR-17-5p functions as a pro-proliferative miRNA in gastric cancer. [•] SOCS6 was demonstrated to be a direct target of miR-17-5p. [•] SOCS6 exerted an opposite function with miR-17-5p in gastric cancer. [•] miR-17-5p acts as a pro-proliferative factor by repressing SOCS6 in gastric cancer. [Copyright &y& Elsevier]

Abstract: PTPRO is often silenced by DNA hypermethylation in primary human tumors and cancer cell lines and functions as a tumor suppressor. Here we show that PTPRO is a target of E2F1. In addition, the microRNA cluster miR-17-92, another target of E2F1, participates in PTPRO regulation. PTPRO mRNA was up-regulated during S phase in synchronized HeLa cells and in vitro PTPRO promoter activity is high in early S phase while the PTPRO 3′UTR reporter activity is low in late S phase. This study provides evidence that the PTPRO gene is co-regulated by both E2F1 and miR-17-92. [Copyright &y& Elsevier]