miRNA-Seq uncovers a link between obesity and breast cancer
Obesity increases breast cancer (BC) risk in post-menopausal women by mostly unknown molecular mechanisms.
In this study, miRNA profiling by RNA-seq was performed in paired benign and malignant biopsies from 12 women at the extremes of the BMI distribution among 83 BC patients. Candidates were validated in all samples by qRT-PCR. 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: 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.
Source: Obesity impacts the regulation of miR-10b and its targets in primary breast tumors. Meerson A et al., BMC Cancer 2019, https://rdcu.be/bhvp3