Past studies have shown that amplified insulin-like growth factor 1 (IGF1)/IGF1 receptor (IGF1-R) signalling has an important role in colorectal cancer (CRC) development, progression and resistance to treatment. In this report, we demonstrate that downregulation of microRNA-497 (miR-497) as a result of DNA copy number reduction is involved in upregulation of IGF1-R in CRC cells. MiR-497 and miR-195 of the miR-15/16/195/424/497 family that share the same 3′ untranslated region (3′UTR) binding seed sequence and are predicted to target IGF1-R were concurrently downregulated in the majority of CRC tissues relative to paired adjacent normal mucosa. However, only overexpression of miR-497 led to suppression of the IGF1-R 3′UTR activity and downregulation of the endogenous IGF1-R protein in CRC cells. This was associated with inhibition of cell survival, proliferation and invasion, and increased sensitivity to apoptosis induced by various stimuli including the chemotherapeutic drugs cisplatin and 5-fluorouracil, and the death ligand tumour necrosis factor-related apoptosis-inducing ligand. The biological effect of miR-497 on CRC cells was largely mediated by inhibition of phosphatidylinositol 3-kinase/Akt signalling, as overexpression of an active form of Akt reversed its impact on cell survival and proliferation, recapitulating the effect of overexpression of IGF1-R. Downregulation of miR-497 and miR-195 appeared to associate with copy number loss of a segment of chromosome 17p13.1, where these miRs are located at proximity. Similarly to miR-195, the members of the same miR family, miR-424 that was upregulated, and miR-15a, miR-15b and miR-16 that were unaltered in expression in CRC tissues compared with paired adjacent normal mucosa, did not appear to have a role in regulating the expression of IGF1-R. Taken together, these results identify downregulation of miR-497 as an important mechanism of upregulation of IGF1-R in CRC cells that contributes to malignancy of CRC.

ABSTRACT. Hepatic pit cells are a population of large granular lymphocytes that substantially contribute to hepatic immunity. Studies have proven that pit cells have a role in liver regeneration, but the details of the relationship between pit cells and liver regeneration is not clear at present. We subjected rats to a two-third hepatectomy; pit cells with high purity were obtained with Percoll density centrifugation and immunomagnetic bead methods, and the changes in mRNA levels in pit cells from the regenerating liver were monitored up to 168 h using a Rat Genome 230 2.0 Array composed of 25,020 distinct rat liver cDNA clones. Of the 25,020 genes analyzed, 612 known and 358 unknown genes were identified to be associated with liver regeneration. The 612 known genes are classified into up-regulation and down-regulation patterns based on the expression levels; they primarily participate in at least 23 biological activities based on gene ontology analysis. Together with gene function enrichment analysis, cytokines and a growth factor-mediated pathway in pit cells were activated at an early phase of liver regeneration; pit cell proliferation occurred from 24-72 h after liver hepatectomy; the machinery of pit cell differentiation commenced early and came into play late; an immune/inflammatory response was enhanced late. Expression pattern analysis of functionally Gene expression and functional analysis of pit cells in rat classified genes in pit cells can give insights into the relationship between pit cells and liver regeneration.