Our findings suggest that SOX2OT may act as a tumor promoter in PDAC through physically binding FUS and regulating its downstream cell cycle-associated factors CCND1 and p27.
Treatment with LGSP resulted in a G1 phase cell cycle arrest in PC3 cells, which was further confirmed by decreasing the expression of cyclin D1 and CDK 4 and increasing the expression of the tumor suppressors p21 and p27.
Thus, monitoring p27 localization and RhoB levels in non-small cell lung carcinoma patients appears to be a powerful prognostic marker for these tumors.
Consistent with the in vitro findings, MYC expression was found to be reduced, while p27 expression was found to be elevated, and BIM expression and cleaved PARP levels were found to be increased in trametinib-treated xenograft tumors.
We demonstrated a positive correlation between mRNA and protein expression of p27 and expression of key metastatic markers, vimentin, snail-2, β-catenin and stathmin-1 (STMN1) in patient tumors.
These effects appear to be mediated by the increase of p21 <sup>waf1</sup> and p27 <sup>Kip1</sup> , associated with a reduction of Cyclin D1 and Rb1 protein phosphorylation, and involve the downregulation of key molecules responsible for tumor development, that is, Notch1, Sox2, Stat3, and Survivin.
In PRL, the deficiency in p21 and p27 contributed to the tumor proliferation and migration and Cdk inhibitors may be used as a new therapeutic approach.
Skp2 (Fbxl1) directly binds to the tumor suppressor p27 in the context of the SCF<sup>Skp2</sup> E3 ubiquitin ligase to ubiquitylate and target-phosphorylated p27 for proteasomal degradation.
In the tumors of p27+/mut rats, the wild-type <i>Cdkn1b</i> allele is neither lost nor silenced, implying that p27 is haploinsufficient for tumor suppression in this model.
Notably, intratumor injection of therapeutic PSMD2 small interfering RNA effectively delayed xenograft tumor growth accompanied by p21 and p27 upregulation.
We show that miR-203-HOTAIR interaction resulted in the inhibition of epithelial-to-mesenchymal transition (EMT) and metastatic genes as indicated by induction of key metastasis-suppressing proteins E-cadherin, claudin (epithelial markers), and PTEN along with induction of tumor suppressor genes p21 and p27.
The present results revealed that genistein exerted its tumor suppressor effect at least partially via inhibition of Skp2 and promotion of its downstream targets p21 and p27.
Pleckstrin homology domain leucine-rich repeat protein phosphatase 2 (PHLPP2) is a tumor suppressor that catalyzes the de-phosphorylation of the AGC kinases, while p27 acts as a tumor suppressor that regulates cell cycle, apoptosis, and cell motility.
In a xenograft mouse model implanted with PC-3-Pa cells, LJ-2618 (3 or 10 mg/kg) effectively inhibited tumor growth with the enhancement of Skp2 degradation and induction of p27 expression in tumor tissues.
TOP2A, Ki67, and cyclin D1, as categorical variables were not predictive, whereas cyclin D1 as continuous variable was predictive of trastuzumab benefit.<b>Conclusions:</b> In TransHERA, patients with HER2-positive early breast cancer with low p27 expression in their tumors benefited from trastuzumab treatment, whereas patients with high p27 expression did not.<i></i>.
Mechanistic studies revealed that G0/G1 arrest and tumor senescence upon pulsed T treatment were associated with a marked decrease in cyclin D1, c-Myc and SKp2, CDK4 and p-Rb levels and upregulation of p27 and p-ERK1/2.
Ectopic miR‑940 accelerated cervical cancer cell growth, proliferation and cell cycle arrest in vitro as well as tumor formation in vivo. p27 and PTEN were evidenced as direct targets for miR‑940 and inhibition of p27 and PTEN recovered the suppressive function of miR‑940-silenced cell towards to proliferation and tumorigenicity in cervical cancer cells.
Moreover, downregulation of CDKN3 and upregulation of p27 inhibited the increase in tumor volume and weight in implanted tumors, decreased the phosphorylation of Akt, and increased the expression of cleaved caspase 3 in tumors.