Currently, resistance to trastuzumab, a human epidermal growth factor receptor 2 (HER2) inhibitor, has become an important obstacle to improving the clinical outcome of patients with advanced HER2+ breast cancer. While cell behavior may be modulated by long non-coding RNAs (lncRNAs), the contributions of lncRNAs within extracellular vesicles (exosomes) are largely unknown. To this end, the involvement and regulatory functions of potential lncRNAs contained within exosomes during the formation of chemoresistance in human breast cancer were investigated. Trastuzumab-resistant cell lines were established by continuously grafting HER2+ SKBR-3 and BT474 cells into trastuzumab-containing culture medium. An lncRNA micro-array assay followed by reverse transcription-quantitative polymerase chain reaction analysis identified that lncRNA-small nucleolar RNA host gene 14 (SNHG14) was upregulated in trastuzumab-resistant cells when compared with parental breast cancer cells. Functional experimentation demonstrated that knockdown of lncRNA-SNHG14 potently promoted trastuzumab-induced cytotoxicity. Furthermore, extracellular lncRNA-SNHG14 was able to be incorporated into exosomes and transmitted to sensitive cells, thus disseminating trastuzumab resistance. Treatment of sensitive cells with exosomes highly expressing lncRNA-SNHG14 induced trastuzumab resistance, while knockdown of lncRNA-SNHG14 abrogated this effect. The Signal Transduction Reporter Array indicated that lncRNA-SNHG14 may promote the effect of trastuzumab by targeting the apoptosis regulator Bcl-2 (Bcl-2)/apoptosis regulator BAX (Bax) signaling pathway. Furthermore, the expression level of serum exosomal lncRNA-SNHG14 was upregulated in patients who exhibited resistance to trastuzumab, compared with patients exhibiting a response. Therefore, lncRNA-SNHG14 may be a promising therapeutic target for patients with HER2+ breast cancer.

Currently, resistance to trastuzumab, a human epidermal growth factor receptor 2 (HER2) inhibitor, has become one major obstacle for improving the clinical outcome of patients with advanced HER2+ breast cancer. While cell behaviour can be modulated by long non‐coding RNAs (lncRNAs), the contributions of lncRNAs in progression and trastuzumab resistance of breast cancer are largely unknown. To this end, the involvement and regulatory functions of lncRNA SNHG14 in human breast cancer were investigated. RT‐qPCR assay showed that SNHG14 was up‐regulated in breast cancer tissues and associated with trastuzumab response. Gain‐ and loss‐of‐function experiments revealed that overexpression of SNHG14 promotes cell proliferation, invasion and trastuzumab resistance, whereas knockdown of SNHG14 showed an opposite effect. PABPC1 gene was identified as a downstream target of SNHG14, and PABPC1 mediates the SNHG14‐induced oncogenic effects. More importantly, ChIP assays demonstrated that lncRNA SNHG14 may induce PABPC1 expression through modulating H3K27 acetylation in the promoter of PABPC1 gene, thus resulting in the activation of Nrf2 signalling pathway. These data suggest that lncRNA SNHG14 promotes breast cancer tumorigenesis and trastuzumab resistance through regulating PABPC1 expression through H3K27 acetylation. Therefore, SNHG14 may serve as a novel diagnostic and therapeutic target for breast cancer patients.

Various microRNAs (miRNAs, miRs) and the forkhead box O (FOXO) family proteins have been shown to influence gastric cancer progression and development. Here, we aimed to identify the gastric cancer related miRNAs and their relationship with the FOXO family. MiRNA profiles were generated by miRNA microarray screening from pre-operative plasma samples. Quantitative reverse transcription PCR and western bolt were used to determine the expression levels of miR-96 and FOXO family. 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide assay and colony formation assay were used to test the cell viability. The miR-96-5p and FOXO3 interaction were confirmed by luciferase reporter assay. Our results demonstrated the excessive expression of miR-96-5p in gastric cancer cell lines and plasma samples from gastric cancer patients. In addition, the protein levels of FOXO3 were decreased in tissue samples from gastric cancer patients. Moreover, miR-96-5p accelerated the gastric cancer cell proliferation by directly targeting FOXO3. Therefore, we conclude that iR-96-5p might promote the progression of gastric cancer by directly targeting FOXO3 mRNA and downregulating the expression of FOXO3 protein, which provides new insights for the molecular mechanism of gastric cancer.

Breast cancer is the most prevalent cancer diagnosed in women and the major malignancy that threatens women health, thus we explored the role of long noncoding RNA LINC01605 in triple‐negative breast cancer (TNBC). We collected tissue samples from TNBC patients and cultured breast cancer cells to detect LINC01605 levels by RT‐PCR. We then constructed LINC01605 knockdown and LINC01605 overexpressed TNBC cell lines, cell proliferation was measured by CCK‐8 and colony formation assays, cell migration and invasion were measured by Transwell assay, and aerobic glycolysis of cells was detected. Furthermore, a downstream target gene was found, and its role was confirmed by mouse allogeneic tumor formation. It discovered that LINC01605 expression was significantly increased in TNBC patients, and its high expression predicted a low survival prognosis for TNBC patients. Stable knockdown of LINC01605 remarkably inhibited cell proliferation, migration, and invasion, as well as aerobic glycolysis by inhibiting lactate dehydrogenase A in TNBC cell lines. Notably, knockdown of LINC01605 suppressed in vivo tumor formation and migration in TNBC transplanted mice. In conclusion, targeting long noncoding RNA LINC01605 might serve as a therapeutic candidate strategy to treat patients with TNBC.