confirmed the upregulation of miR-424-5p expression level in PDAC cells by quantitative RT-PCR and found that the high expression of miR-424-5p suppressed the expression of cytokine-induced signaling 6 (SOCS6), leading to increased proliferation, migration and invasion of pancreatic cancer cells, and inhibited cell apoptosis .
He et al., "MicroRNA-424-5p suppresses the expression of SOCS6 in pancreatic cancer," Pathology & Oncology Research, vol.
Indeed, CIS and SOCS2, SOCS1 and SOCS3, SOCS4 and SOCS5, and SOCS6 and SOCS7 all form related pairs .
For example, CIS, SOCS1, SOCS2, and SOCS3 have relatively short (50-80 residues) N-terminal regions, whereas SOCS4, SOCS5, SOCS6 and SOCS7 have longer N-terminal regions of up to 380 residues [22, 25, 26].
Considerably less work has been done on the remaining two pairs of SOCS proteins, SOCS4 and 5 and SOCS6 and 7.
and degradation of target proteins , using specific interaction with an alternate E3 ligase component named heme-oxidised IRP2 ubiquitin ligase-1 (HOIL-1) , and as SOCS2, SOCS6 also has the ability to degrade other SOCS proteins, including SOCS7 .
SOCS6 has been shown to inhibit pathways downstream of the insulin and IGF-I receptors .
However, SOCS5 transgenic mice were found to have increased peritoneal IL2 and IFN-[gamma], cytokines involved in the promotion of Th1 differentiation , and SOCS6 was shown to bind to the kinase domain of active [p56.sup.lck], targeting it for ubiquitination and subsequent degradation, with SOCS6 overexpression resulting in repression of TCR-dependent IL-2 promoter activity .
Interestingly, SOCS3 represents a good example that SOCS family tumour suppressor activity may not be solely due to their negative feedback role in the JAKSTAT signalling (the other examples are SOCS6 and SOCS7; see below).