Abstract 3393: miR-34b: A regulator of VEGF-A, Notch1 and Bcl-2 in thyroid carcinoma
Authors: Maroof Hamidreza , Salajegheh Ali , Lam. Alfred KY 
Published: July 2016

Background: Thyroid cancer is the most common endocrine malignancy accounting for &gt;91% of endocrine malignancy and 1.8% of all recently distinguished cancer reports, with an incidence continuing to rise globally in recent decades and current treatment strategies are not potent enough for patients. Therefore, novel and more effective treatment are outstandingly required. New strategy for treatment is target therapy, which not only hold cancer-specific expression but also limits side effects. miR-34b as part of p53 tumor suppressor network, plays crucial role in many physiological and pathological processes including cancer initiation, tumor progression and cancer angiogenesis process.

Objectives: In this study, we evaluate the functional roles of miR-34b in 2 thyroid cancer cell lines for its potential in modulating angiogenesis and proliferation in thyroid malignancies.

Methods: Expression levels of miR-34b was determined in metastasizing human papillary thyroid carcinoma (B-CPAP) and human undifferentiated thyroid carcinomas (MB-1) cell lines by qPCR. Exogenous miR-34b was transfected to thyroid cancer cell lines to investigate its effect on predominant genes involved in angiogenesis, cell cycle and apoptosis regulation including VEGF-A and Bcl-2 and Notch1. Confocal laser scanning microscopy (CLSM) and western blot techniques were performed to illustrate the protein expression changes. To demonstrate the perturbation of cell cycle and apoptosis pathways through exogenous miR-34b, fluorescence-activated cell sorting (FACS) was performed.

Results: Significant underexpression of miR-34b was established in B-CPAP and MB-1 cell lines while outstanding overexpression of VEGF-A, Bcl-2 and Notch1 were detected. After transfection with miR-34b, significant drop in concentration of VEGF-A, Bcl-2 and Notch1 were noticed compared with controls in CLSM and western blot analysis (p&lt; 0.05).

Cell cycle analysis demonstrated that 48 hours after ectopic induction of miR-34b, significant impairment in proliferation of B-CPAP and MB-1 was induced through arresting cancer cell proliferation in G0-G1 phase (14.27% ±3.50 for B-CPAP and 13.61% ±0.16 for MB-1) (p&lt;0.05). Apoptosis assay also revealed that miR-34b, induced cell death by increasing early and late apoptosis events, compared with controls (2.20% ±0.16 for B-CPAP and 7.87% ±0.92 for MB-1) (p&lt;0.05).

Conclusion: These results pave the way that miR-34b may be involved in balancing tumour angiogenesis, cell proliferation and apoptosis in thyroid cancer. These could potentially occur via direct modulation of downstream targets such as VEGF-A, Bcl-2 and Notch1 for their role in those events. The future of this research will investigate the regulatory role of miR-34b in Papillary and undifferentiated thyroid carcinoma through larger scale in vivo and clinical trial studies which shall potentially improve the clinical presentation of aggressive malignancies.

Citation Format: Hamidreza Maroof, Ali Salajegheh, Alfred KY Lam. miR-34b: A regulator of VEGF-A, Notch1 and Bcl-2 in thyroid carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3393.