This research aims to investigate the effect of lncRNA KB-1980E6.3 on the biological behaviour of breast cancer cells under normoxic conditions and the underlying molecular mechanism. The expression of KB-1980E6.3 in breast cancer tissues and cells was detected by RT-qPCR. The proliferation, migration and invasion of cells were evaluated by CCK-8, colony formation, scratch and Transwell assays; KB-1980E6.3-related xenograft models were established for in vivo studies. The protein expression of PI3K, p-PI3K, AKT and p-AKT was validated by western blotting analysis. The levels of KB-1980E6.3 are significantly upregulated in breast cancer tissues and cells and are related to the poor prognosis. Functional research both in vivo and in vitro revealed that the downregulation of KB-1980E6.3 expression significantly decreased cell proliferation, invasion and migration, while ectopic KB-1980E6.3 expression obviously promoted these biological phenotypes. In terms of the mechanism, KB-1980E6.3 is involved in the activation of the PI3K/AKT signalling pathway. Knockdown of KB-1980E6.3 reduced the expression of the p-PI3K and p-AKT proteins, whereas KB-1980E6.3 overexpression showed the opposite result. The agonist 740Y-P and inhibitor LY294002 reversed the effect of KB-1980E6.3 knockdown and overexpression on the PI3K/AKT pathway in BC cells. KB-1980E6.3 promotes the proliferation, invasion and migration of breast cancer cells by activating PI3K/AKT signalling, which can be used as a potential target for breast cancer therapy.

BACKGROUND:Numerous studies have reported on the genetic factors related to asthma. In recent years, the vitamin D receptor (VDR) has been identified as one of the asthma susceptibility genes that is closely associated with the pathogenesis of asthma. METHODS:Randomized controlled trials (RCTs) related to asthma and the VDR were identified from the Chinese and English databases. The following keywords were used as search terms: "asthma", "vitamin D receptor", "VDR", "polymorphism", and "mutation". Meta-analysis was performed using RevMan 5.3 and Stata 13 software provided by the Cochrane system. RESULTS:A total of 7 RCTs were included in this meta-analysis, 6 of which described the correct random allocation methods, 6 described the allocation plan in detail, and 4 used the blinding method. The frequency of the CC + CA dominant genotype at the Apa I locus and the GG + GA genotype frequency at the Bsm I locus of the VDR gene were significantly higher in asthmatic patients compared to control healthy patients [odds ratio (OR) =0.81, 95% confidence interval (CI): 0.68 to 0.98, P=0.03<0.05; and OR =2.05, 95% CI: 1.23 to 3.41, P=0.006<0.05, respectively]. There were no significant differences between the CC, CT, and TT genotype frequencies at the Fok I site of the VDR gene in the experimental group and the CC, CT, TT genotype frequencies at the Taq I site and the control group (P>0.05). There was no significant difference between the genotype frequencies. DISCUSSION:Meta-analysis confirmed that VDR gene polymorphisms are closely related to the onset of asthma, and the gene expression of the Fok I, Bsm I, Apa I, and Taq I loci directly affects the incidence of asthma.

Tamoxifen (TAM) resistance constitutes a challenge in managing estrogen receptor (ER)α+ breast cancer patients. G-protein-coupled estrogen receptor (GPR30/GPER), which reportedly initiates TAM resistance in ERα+/ GPR30+ breast cancers, is detected in the breast cancer microenvironment, especially cancer associated fibroblasts (CAFs). Herein, considering that GPR30 mediates transcriptional regulation in different cell backgrounds, a microarray strategy was applied in immortalized CAFs derived from primary breast cancer samples, resulting in the identification of 165 GPR30 target genes, among which HMGB1 was confirmed to be upregulated by 17-β estradiol(E2)- and TAM-triggered GPR30 activation in CAFs. Activated GPR30 increased extracellular HMGB1 secretion by CAFs, which was reduced by blocking PI3K/AKT signaling using G15 or LY294002. GPR30-induced HMGB1 upregulation triggered MEK/ERK signaling, leading to increased autophagic behavior to protect cancer cells from TAM-induced apoptosis, mimicking the recombinant HMGB1-mediated increase in cancer cell resistance potential to TAM. MEK/ERK signaling blockage by U0126 decreased the autophagic behavior and resistance ability of cancer cells to TAM. CAF-expressed GPR30 induced TAM resistance via HMGB1 in vivo. Overall, TAM upregulated HMGB1 expression and secretion in CAFs via GPR30/PI3K/AKT signaling, and the secreted HMGB1 induced autophagy to enhance TAM resistance in MCF-7 cells in an ERK-dependent manner. Thus, targeting GPR30 and downstream cascades may be an effective strategy to attenuate the resistance of ERα-positive breast tumors to endocrine therapy.

To aim of this was to observe emodin-mediated cytotoxicity and its influence on Rad51 and ERCC1 expressionin non-small cell lung cancer (NSCLC). NSCLC cells were cultured in vitro with emodin at various concentrations (0, 25, 50, 75 and 100 μmol/L) for 48 h and the proliferation inhibition rate was determined by the MTT method. Then, NSCLC were treated with emodin (SK-MES-1 40 μmol/L, A549 70 μmol/L) or 20 μmol/L U0126 (an ERK inhibitor) for 48 h, or with various concentrations of emodin for 48 h and the protein and mRNA expressions of ERCC1 and Rad51 were determined by RT-PCR and Western blot assay, respectively. Emodin exerted a suppressive effect on the proliferation of NSCLC in a concentration dependent manner. Protein and mRNA expression of ERCC1 and Rad51 was also significantly decreased with the dose. Vacuolar degeneration was observed in A549 and SK-MES-1 cell lines after emodin treatment by transmission electron microscopy. Emodin may thus inhibited cell proliferation in NSCLC cells by downregulation ERCC1 and Rad51.

To investigate the role of ERK1, c-Jun, c-Myc and Cyclin D1 in the suppressive effect of ursolic acid (UA) on the proliferation of human umbilical vein endothelial cells (HUVECs), HUVECs were treated in vitro with UA at various concentrations (31.5, 62.5, 125, 250 and 500 mu g/ml) for different durations (12, 24 and 48 h) and the proliferation inhibition rate of HUVECs was determined by MTT method. Then, HUVECs were treated with 125 mu g/ml UA or 100 mu mol/L PD98059 (an ERK inhibitor) for 48 h, or with various concentrations of UA for 24 h; or with 125 mu g/ml UA for different durations and the protein and mRNA expressions of ERK1, c-Jun, c-Myc and Cyclin D1 were determined by RT-PCR and Western blot assay, respectively. UA exerted a suppressive effect on the proliferation of HUVECs in a time and concentration dependent manner. The protein and mRNA expressions of ERK1, c-Jun, c-Myc and Cyclin D1 in HUVECs were significantly decreased following treatment with UA and PD98059, which was also in a concentration and time dependent manner. UA can inhibit the proliferation of HUVECs by inhibiting the ERK signaling pathway.