Obesity impacts the regulation of miR-10b and its targets in primary breast tumors.

BACKGROUND: Obesity increases breast cancer (BC) risk in post-menopausal women by mostly unknown molecular mechanisms which may partly be regulated by microRNAs (miRNAs). METHODS: We isolated RNA from paired benign and malignant biopsies from 83 BC patients and determined miRNA profiles in samples from 12 women at the extremes of the BMI distribution by RNA-seq. Candidates were validated in all samples. Associations between miR-10b expression and validated target transcript levels, and effects of targeted manipulation of miR-10b levels in a primary BC cell line on proliferation and invasion potential, were explored. RESULTS: Of the 148 miRNAs robustly expressed in breast tissues, the levels of miR-21, miR-10b, miR-451a, miR-30c, and miR-378d were significantly associated with presence of cancer. Of these, miR-10b showed a stronger down-regulation in the tumors of the obese subjects, as opposed to the lean. In ductal but not lobular tumors, significant inverse correlations were observed between the tumor levels of miR-10b and miR-30c and the mRNA levels of cancer-relevant target genes SRSF1, PIEZO1, MAPRE1, CDKN2A, TP-53 and TRA2B, as well as tumor grade. Suppression of miR-10b levels in BT-549 primary BC-derived cells increased cell proliferation and invasive capacity, while exogenous miR-10b mimic decreased invasion. Manipulation of miR-10b levels also inversely affected the mRNA levels of miR-10b targets BCL2L11, PIEZO1 and NCOR2. CONCLUSIONS: Our findings suggest that miR-10b may be a mediator between obesity and cancer in post-menopausal women, regulating several known cancer-relevant genes. MiR-10b expression may have diagnostic and therapeutic implications for the incidence and prognosis of BC in obese women.

Sex-related gonadal gene expression differences in the Russian sturgeon (Acipenser gueldenstaedtii) grown in stable aquaculture conditions.

The Russian sturgeon (Acipenser gueldenstaedtii) is a primitive freshwater fish and a source of caviar. In the present study, the gonadal transcriptomes of male and female Russian sturgeons grown in stable aquaculture conditions were analyzed. RNA sequencing of whole-gonad transcriptomes from pools of 4-year old fish (five females, four males), resulted in the identification of 28,170 unique transcripts. Of these, 16,191 could be annotated by similarity to gene sequences from other species. There were 392 transcripts that showed differential abundance by a factor of 20-fold or more between the sexes; 272 of these were annotated; of these, 175 and 97 were in greater abundance in ovaries and testes, respectively. Functional annotation and clustering of the genes with differential abundances of mRNA allowed for identification of several clusters. Thus, a group of transcriptional regulators and factors involved in cell division, especially septins, were in greater abundance in the ovaries; while a different set of transcription factors (including sox6 and sox30) and a group of protein kinases were in greater abundance in the testes. The transcript abundances of nine highly abundant candidate transcripts, as well as of two additional genes previously known to be involved in reproduction, cyp19 (p450 aromatase) and foxl2, were assessed in the individual samples by qRT-PCR. Of these, five (including cyp19 and foxl2) were in greater abundance in ovaries, while the abundance of ighm1 mRNA was greater in testes. Phylogenetic analysis based on the k1c18 keratin gene placed the sturgeon sequence nearest those of other primitive fish species, supporting the ancient origin of the sturgeon. In conclusion, this study details transcriptome differences between male and female sturgeon and identifies key genes that may contribute to sexual determination and differentiation.