LncRNA ST8SIA6-AS1 promotes proliferation, migration and invasion in breast cancer through the p38 MAPK signalling pathway.

Long non-coding RNAs (lncRNAs) are regarded as important functional regulators of various biological processes and are also known to be involved in the occurrence and development of human cancers, including breast cancer (BC). In our present study, the RNA expression profiling data for a large cohort of human BC samples were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and the differentially expressed lncRNAs were screened out. We found that the expression of ST8SIA6-AS1 was elevated in BC tumour tissues compared with the adjacent normal tissues in the samples from the TCGA and GEO datasets, as well as in 138 BC tissue samples obtained by us. The high expression of ST8SIA6-AS1 was associated with estrogen receptor-negative, progesterone receptor-negative, advanced tumour-node-metastasis stage and worse survival in BC patients. In vitro functional studies revealed that high expression of ST8SIA6-AS1 promoted proliferation, invasion and migration of BC cell lines. The results of the in vivo studies indicated that upregulation of ST8SIA6-AS1 promoted xenograft tumour growth of BC. Mechanistically, ST8SIA6-AS1 regulated AKT1 and p38 mitogen-activated protein kinase (MAPK) gene expression by affecting their mRNA and protein levels, respectively, and it also affected the phosphorylation of AKT1 protein. Rescue experiments indicated that ST8SIA6-AS1 promoted BC cell proliferation, invasion and migration in a p38 MAPK signalling-mediated manner. Together, our data suggest that ST8SIA6-AS1 plays an important role in the occurrence and development of BC and may therefore serve as a promising therapeutic target.

Med19 is involved in chemoresistance by mediating autophagy through HMGB1 in breast cancer.

Adriamycin (ADM)-based regimens are the most effective chemotherapeutic treatments for breast cancer. However, intrinsic and acquired chemoresistance is a major therapeutic problem. Our goal was to clarify the role of mediator complex subunit 19 (Med19) in chemotherapy resistance and to elucidate the related molecular mechanisms. In this study, ADM-resistant human cells (MCF-7/ADM) and tissues exhibited increased Med19 expression and autophagy levels relative to the corresponding control groups. Additionally, MCF-7/ADM cells showed changes in two selective markers of autophagy. There was a dose-dependent increase in the light chain 3 (LC3)-II/LC3-I ratio and a decrease in sequestosome 1 (P62/SQSTMl) expression. Furthermore, lentivirus-mediated Med19 inhibition significantly attenuated the LC3-II/LC3-I ratio, autophagy-related gene 3 (Atg3) and autophagy-related gene 5 (Atg5) expression, P62 degradation, and red fluorescent protein-LC3 dot formation after treatment with ADM or rapamycin, an autophagy activator. Furthermore, the antiproliferative effects of ADM, cisplatin (DDP), and taxol (TAX) were significantly enhanced after suppressing Med19 expression. Notably, the effects of Med19 on autophagy were mediated through the high-mobility group box-1 (HMGB1) pathway. Our findings suggest that Med19 suppression increased ADM chemosensitivity by downregulating autophagy through the inhibition of HMGB1 signaling in human breast cancer cells. Thus, the regulatory mechanisms of Med19 in autophagy should be investigated to reduce tumor resistance to chemotherapy.

hsa_circRNA_0006528 as a competing endogenous RNA promotes human breast cancer progression by sponging miR-7-5p and activating the MAPK/ERK signaling pathway.

Emerging research has indicated that circular RNAs (circRNAs), a novel class of non-coding RNAs, play a vital role in human tumorigenesis and progression. Our previous results suggested that hsa_circ_0006528 (circ_0006528), a circRNA with an unknown function, mediates adriamycin resistance in human breast cancer cells. However, the role of circ_0006528 in breast cancer progression remains unknown. Here, we investigated the probable involvement of circ_0006528 in breast cancer. We analyzed a cohort of 97 patients and found that circ_0006528 expression was significantly upregulated in human breast cancer tissues compared with that in adjacent non-tumorous tissues and was significantly associated with advanced tumor-node-metastasis (TNM) stage and poor prognosis. In addition, we found that in breast cancer cells, circ_0006528 could promote DNA synthesis and cell proliferation, invasion, and migration. Downregulating circ_0006528 induced G2 phase arrest and cell apoptosis. Further mechanistic studies revealed that circ_0006528 could sponge endogenous miR-7-5p and inhibit its activity. We also identified Raf1, which activates the MAPK/ERK signaling pathway, as a target of miR-7-5p and determined that circ_0006528 promotes breast cancer growth, invasion, and migration by promoting the expression of Raf1 and activates the MAPK/ERK pathway. Thus, this study provides the first evidence of the circ_0006528/miR-7-5p/Raf1/MEK/ERK regulatory network in the development of breast cancer and suggests that circ_0006528 is a potential therapeutic target and prognostic predictor for breast cancer.

Differences in metabonomic profiles of abdominal subcutaneous adipose tissue in women with polycystic ovary syndrome.

Introduction: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that often coexists with a metabolic disorder. Studies have demonstrated that the malfunction of adipose tissue, particularly abdominal adipose tissue, could exacerbate reproductive and metabolic problems in PCOS patients. Adipose tissue-secreted signaling mediators (e.g., lipids and metabolites) would then interact with other body organs, including the ovary, to maintain the systemic equilibrium. Methods: In this study, we examined adipose samples from PCOS patients and unaffected individuals using a liquid chromatography-mass spectrometry-based metabonomics approach (LC-MS/MS). PCOS biomarkers were selected using multivariate statistical analysis. Results: Our pathway analysis revealed that these differential metabolites could be engaged in inflammatory diseases and mitochondrial beta-oxidation. We further developed an in vitro PCOS cell model to examine the effects of hyperandrogenism on granulosa cells and related metabolic disorders. We noted that isoleucine recovered the promotive effect on cell apoptosis, inhibitory effect on cell proliferation, sex hormone secretion, and mitochondrial function induced by dehydroepiandrosterone. Our gas chromatography-mass spectrometry targeted analysis (GC-MS/MS) revealed that isoleucine was significantly decreased in PCOS patients. Discussion: Based on these results, we speculate that metabolome alterations are vital in ameliorating PCOS symptoms. This may be a novel therapeutic target for PCOS treatment. Our study provides preliminary evidence that these findings will enhance our ability to accurately diagnose and intervene in PCOS.

Med19 is targeted by miR-101-3p/miR-422a and promotes breast cancer progression by regulating the EGFR/MEK/ERK signaling pathway.

Our previous study found that mediator complex subunit 19 (Med19) is upregulated and involved in breast cancer tumorigenesis; however, the detailed effects and mechanism of Med19 in breast cancer require further study. In this study, we found that Med19 was obviously elevated in human breast cancer tissues, which was significantly associated with larger tumors, high-grade malignant features and poor prognosis. Furthermore, Med19 enhanced breast cancer cell proliferation, epithelial-mesenchymal transition, invasion and migration in vitro and in vivo. Med19 interacted with epidermal growth factor receptor (EGFR) and increased EGFR expression. Moreover, Med19 activated the EGFR/mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway and exerted its oncogenic activity in an EGFR signaling-mediated manner. In addition, Med19 expression was regulated by miR-101-3p and miR-422a. Med19 expression positively correlated with EGFR expression and negatively correlated with miR-101-3p and miR-422a expression in human breast cancer tissues. Med19 mediated the crosstalk between miR-101-3p/miR-422a and the EGFR/MEK/ERK signaling pathway. This study revealed a new miR-101-3p/miR-422a-Med19-EGFR/MEK/ERK axis that plays a significant role in breast cancer progression. These results help elucidate the potential mechanisms of Med19 in human breast cancer progression.

Screening circular RNA related to chemotherapeutic resistance in breast cancer.

AIM: We aimed to identify circular RNAs (circRNAs) associated with breast cancer chemoresistance. MATERIALS & METHODS: CircRNA microarray expression profiles were obtained from Adriamycin (ADM) resistant MCF-7 breast cancer cells (MCF-7/ADM) and parental MCF-7 cells and were validated using quantitative real-time reverse transcription PCR. The expression data were analyzed bioinformatically. RESULTS: We detected 3093 circRNAs and identified 18 circRNAs that are differentially expressed between MCF-7/ADM and MCF-7 cells; after validating by quantitative real-time reverse transcription PCR, we predicted the possible miRNAs and potential target genes of the seven upregulated circRNAs using TargetScan and miRanda. The bioinformatics analysis revealed several target genes related to cancer-related signaling pathways. Additionally, we discovered a regulatory role of the circ_0006528-miR-7-5p-Raf1 axis in ADM-resistant breast cancer. CONCLUSION: These results revealed that circRNAs may play a role in breast cancer chemoresistance and that hsa_circ_0006528 might be a promising candidate for further functional analysis.

[Identification of Vibrio campbellii isolated from cultured pacific oyster].

Four bacterial strains were isolated from cultured pacific oyster (Crassostrea gigia) in September 2003 at coast of Fujian province. Their morphological, physiological and biochemical characteristics and 16S rRNA sequence were analyzed. And the relationship between reproduction of the bacterium and NaCl concentrations, pH and temperature were also determined. The results showed that four strains were gram-negative rods with a single polar flagellum, glucose fermented without gas production, oxidase positive, required sodium ions for growth, no pigment, non-luminescence; They grew well on TCBS-plate as green colonies and were sensitive to the vibriostratic agent O/129. Therefore, it was confirmed that the strains belonged to the genus of Vibrio. The sequence analysis of 16S rRNA gene of SXS1 isolation and comparison with that of other related vibrios- showed that SXS1 was very close to Vibrio campbellii. The similarities was 99%. The distribution of V. campbellii in environment and its relationship to the diseases of aquaculture animals were discussed.