Trastuzumab resistance is leading cause of mortality in HER2-positive breast cancers, and the role of TGF-β-induced epithelial-mesenchymal transition (EMT) in trastuzumab resistance is well established, but the involvement of lncRNAs in trastuzumab resistance is still unknown. Here, we generated trastuzumab-resistant breast cancer cells with increased invasiveness compared with parental cells, and observed robust epithelial–mesenchymal transition (EMT) and consistently elevated TGF-β signaling in these cells. We identified long noncoding RNA activated by TGF-β (lnc-ATB) was the most remarkably upregulated lncRNA in TR SKBR-3 cells and the tissues of TR breast cancer patients. We found that lnc-ATB could promote trastuzumab resistance and invasion-metastasis cascade in breast cancer by competitively biding miR-200c, up-regulating ZEB1 and ZNF-217, and then inducing EMT. In addition, we also found that the high level of lnc-ATB was correlated with trastuzumab resistance of breast cancer patients. Thus, these findings suggest that lncRNA-ATB, a mediator of TGF-β signaling, could predispose breast cancer patients to EMT and trastuzumab resistance.

Aquaporins are water channel proteins that facilitate the passage of water through biological membranes and play a crucial role in plant growth. We show that ethylene treatment significantly reduced petal size, inhibited expansion of petal abaxial subepidermal cells, and decreased petal water content in rose (Rosa hybrida 'Samantha'). Here, we report the isolation of a plasma membrane aquaporin (PIP) gene, Rh-PIP2;1, and characterized its potential role in ethylene-inhibited petal expansion. Rh-PIP2;1 is mainly localized on the plasma membrane and belongs to the class 2 subfamily of PIP proteins. We show that Rh-PIP2;1 is an active water channel. The transcripts of Rh-PIP2;1 are highly abundant in petal epidermal cells, especially in the abaxial subepidermal cells. The expression of Rh-PIP2;1 is highly correlated with petal expansion and tightly down-regulated by ethylene. Furthermore, we demonstrate that in Rh-PIP2;1-silenced flowers, petal expansion was greatly inhibited and anatomical features of the petals were similar to those of ethylene-treated flowers. We argue that Rh-PIP2;1 plays an important role in petal cell expansion and that ethylene inhibits petal expansion of roses at least partially by suppressing Rh-PIP2;1 expression.

Tumour metastasis, the spread of cancer cells from the original tumour site followed by growth of secondary tumours at distant organs, is the primary cause of cancer-related deaths and remains poorly understood. Here we demonstrate that inhibition of CDK4/6 blocks breast tumour metastasis in the triple-negative breast cancer model, without affecting tumour growth. Mechanistically, we identify a deubiquitinase, DUB3, as a target of CDK4/6; CDK4/6-mediated activation of DUB3 is essential to deubiquitinate and stabilize SNAIL1, a key factor promoting epithelial–mesenchymal transition and breast cancer metastasis. Overall, our study establishes the CDK4/6–DUB3 axis as an important regulatory mechanism of breast cancer metastasis and provides a rationale for potential therapeutic interventions in the treatment of breast cancer metastasis.

The Ginkgo biloba extract (GBE) has been reported to have a wide range of health benefits in traditional Chinese medicine. The aim of this study was to evaluate the antihyperglycemic effects of GBE on streptozotocin- (STZ-) induced diabetes in rats. Diabetes was induced in male Wistar rats by the administration of STZ (60 mg/kg b.w.) intraperitoneally. GBE (100, 200, and 300 mg/kg b.w.) was administered orally once a day for a period of 30 days. Body weight and blood glucose levels were determined in different experimental days. Serum lipid profile and antioxidant enzymes in hepatic and pancreatic tissue were measured at the end of the experimental period. Significant decreases in body weight and antioxidant ability and increases in blood glucose, lipid profile, and lipid peroxidation were observed in STZ-induced diabetic rats. The administration of GBE and glibenclamide daily for 30 days in STZ-induced diabetic rats reversed the above parameters significantly. GBE possesses antihyperglycemic, antioxidant, and antihyperlipidemia activities in STZ-induced chronic diabetic rats, which promisingly support the use of GBE as a food supplement or an adjunct treatment for diabetics.

Accumulating evidence has highlighted the important roles of long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) in tumor biology. However, the roles of cancer specific lncRNAs in lncRNA-related ceRNA network of lung adenocarcinoma (LUAD) are still unclear. In the present study, the 465 RNA sequencing profiles in LUAD patients were obtained from the cancer genome atlas (TCGA) database, which provides large sample RNA sequencing data free of charge, and 41 cancer specific lncRNAs, 25 miRNAs and 1053 mRNAs (fold change >2, p<0.05) were identified. Then, the lncRNA-miRNA-mRNA ceRNA network of LUAD was constructed with 29 key lncRNAs, 24 miRNAs and 72 mRNAs. Subsequently, we selected these 29 key lncRNAs to analyze their correlation with clinical features, and 21 of them were aberrantly expressed with tumor pathological stage, TNM staging system, lymph node metastasis and patient outcome assessment, respectively. Furthermore, there were 5 lncRNAs (BCRP3, LINC00472, CHIAP2, BMS1P20 and UNQ6494) positively correlated with overall survival (OS, log-rank p<0.05). Finally, 7 cancer specific lncRNAs were randomly selected to verify the expression in 53 newly diagnosed LUAD patients using qRT-PCR. The expression results between TCGA and qRT-PCR were 100% in agreement. The correlation between AFAP1-AS1 and LINC00472 and clinical features were also confirmed. Thus, our results showed the lncRNA expression profiles and we constructed an lncRNA-miRNA-mRNA ceRNA network in LUAD. The present study provides novel insight for better understanding of lncRNA-related ceRNA network in LUAD and facilitates the identification of potential biomarkers for diagnosis and prognosis.