Our data suggested that the promoted cell proliferation, G1/S cell cycle progression, and the enhanced expression of β-catenin Cyclin D1 and C-myc while reduced P27 induced by the overexpression of USP6NL were significantly reversed by additional treatment of XAV939, indicating that activating Wnt/β-catenin pathway was the mechanism, by which USP6NL exerted carcinogenesis in CRC in vitro.
Moreover, although the absence of RhoB promoted tumorigenesis in p27<sup>-/-</sup> animals, it had no effect in p27<sup>CK-</sup> knock-in mice, suggesting that cytoplasmic p27 may act as an oncogene, at least in part, by inhibiting the activity of RhoB.
Taken together, this finding suggests P21 and P27 promote carcinogenesis and development in seminal vesicles of TRAMP mice via accelerating cell cycle progression, in which oncogenic transformation of P21 and P27 might be through regulation of EGFR-AKT signaling.
Our results thereby indicate that loss of PCBP1 expression firstly attenuates p27 expression at post-transcriptional level, and subsequently promotes carcinogenesis.
The results showed that p27, CDK6, and CCND1 played different roles in tumorigenesis and development, which are in accordance with CDK6 and CCND1 in affecting the cell cycle and cell proliferation. p27 regulated the cell cycle and inhibited cell proliferation by affecting formation of the cell cycle-dependent complex CDK6/CCND1, but did not directly affect the expression of CDK6 and CCND1.
Here we identify pRb and p53 doubly deficient (DKO) prostate tumorigenesis as a context in which p27 ubiquitination by SCF<sup>Skp2/Cks1</sup> is required for p27 downregulation. p27 protein accumulated in prostate when p27T187A KI mice underwent DKO prostate tumorigenesis. p27T187A KI or Skp2 knockdown (KD) induced similar degrees of p27 protein accumulation in DKO prostate cells, and Skp2 KD did not further increase p27 protein in DKO prostate cells that contained p27T187A KI (AADKO prostate cells). p27T187A KI activated an E2F1-p73-apoptosis axis in DKO prostate tumorigenesis, slowed disease progression and significantly extended survival.
We found miR-1307 was overexpressed in prostate cancer cells and tissues, overexpression of miR-1307 significantly promoted cell proliferation and tumorigenesis in vitro investigated by MTT assay, colony formation assay and soft agar growth assay, meanwhile overexpression of miR-1307 inhibited cell cycle inhibitors p21 and p27 both in mRNA and protein levels.
Concomitant knockdown of E6AP and p27 partially restores PC cell growth, supporting the contribution of p27 to the overall effect of E6AP on prostate tumorigenesis.
Collectively, these results demonstrate that SIRT1 suppression of p27 is required for KSHV-induced tumorigenesis and identify a potential therapeutic target for KS.
The association between high expression of c-Myc and SKP2 with low expression of P27 suggested that the Skp2-P27 pathway may play an important role in ovarian carcinogenesis.
Exogenous expression of UTF1 resulted in the significant inhibition of cell proliferation in vitro and tumorigenesis in vivo through attenuating cell cycle arrest via increasing the level of p27 (Kip1) .
Here, we report that impairment in p27 IRES-mediated translation due to decreased levels of DKC1 activity markedly increases spontaneous pituitary tumorigenesis in p27 heterozygous mice.
Urethane-induced lung tumors in mice frequently harbor mutations in the Kras oncogene, and in this study, we use this model to address the regulation of p27 during tumorigenesis.