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Triple-negative breast cancer (TNBC) stands for a refractory subtype, which predicts poor prognosis and has no effective therapies yet for improving it. Given the restrictions of traditional treatments, novel therapeutic strategies need excavating to alleviate the intrinsic or acquired resistance. Ribociclib, a selective CDK4/6 inhibitor, has successfully prevented cancers from deteriorating by intervening the CDK4/6-cyclin D-Rb-E2F pathway, especially for estrogen receptor-positive (ER +) breast cancer. However, there still remains limited accessibility referring to TNBC. Performing experiments on MDA-MB-231 cells, we found that LEE011 could suppress cell proliferation, and this suppression tended to be dose-dependently. Western blotting analysis presented significant decrease with the expression of CDK4/6 after LEE011 treated, and other proteins associated with this axis such as cyclin D1, p-Rb, Rb, E2F1 showed aberrant changes. Moreover, LEE011 induced G0–G1 phase cell cycle arrest, promoted cell apoptosis, and reduced cell migration in vitro. In addition, tumor growth was remarkably impeded without obvious side-effects in MDA-MB-231 xenograft models. Our research has identified that LEE011 was not completely invalid for MDA-MB-231. Considering its pivotal status in TNBC, the CDK4/6-cyclin D-Rb-E2F pathway informed us the possibility and practicality of Ribociclib (LEE011) as pharmacological intervention, but challenges warrant further validation in prospective studies. [ABSTRACT FROM AUTHOR]

Considering the role of variants in the 3′ untranslated region (3′UTR) of GPR30 gene remains unclear, we analyzed the association between the variants at the GPR30 gene 3′UTR miRNA binding sites and their mRNA expression using the data from the HapMap online database. Nine single nucleotide polymorphisms (SNPs) in GPR30 gene 3′UTR had available minor allele frequency (MAF) values which were obtained. And the frequency distribution of all the selected GPR30 gene 3′UTR variants genotypes among the different populations and pairwise linkage disequilibrium (LD) values were calculated. In addition, correlation analysis of the selected GPR30 variants genotypes and their mRNA expression in the lymphoblastoid cell lines was performed, which showed that only rs10235056 was significantly associated with GPR30 mRNA expression ( p = 0.028), but rs4266553 ( p = 0.304), rs3808353 ( p = 0.900), rs3808354 ( p = 0.739) and rs1133043 ( p = 0.913) were insignificant. Taken together, the present study provides the first evidences that the GPR30 rs10235056 A > G polymorphism could be a putative variant mediating its post-transcriptional regulation, which might support its use as markers of cancer risk and individualized treatment. [ABSTRACT FROM AUTHOR]