Decreased serum exosomal miR-29a expression and its clinical significance in papillary thyroid carcinoma.

BACKGROUND: Aberrant levels of circulating microRNAs (miRNAs) are potential biomarkers in papillary thyroid carcinoma (PTC) diagnosis and therapy. The aim of this study was to evaluate serum exosomal miR-29a expression as a non-invasive biomarker for PTC diagnosis and prognosis. METHODS: Quantitative reverse transcription polymerase chain reaction was applied to measure serum exosomal miR-29a expression levels in blood samples of 119 patients with PTC and 100 control subjects. RESULTS: Serum exosomal miR-29a expression levels were significantly decreased in PTC cases. In addition, receiver operating characteristic (ROC) analysis revealed serum exosomal miR-29a could well differentiate PTC from normal controls. Moreover, serum exosomal miR-29a levels increased progressively and significantly 30 days and 90 days after surgery. Furthermore, PTC patients with lower serum exosomal miR-29a expression had higher risk of recurrence. Decreased serum exosomal miR-29a expression was significantly associated with worse clinical variables including tumor size, extrathyroidal extension, and TNM stage, as well as shorter survival. Finally, both univariate and multivariate identified serum exosomal miR-29a as an independent prognostic indicator for overall survival. CONCLUSION: These results demonstrated that serum exosomal miR-29a might serve as a potential biomarker for PTC diagnosis and prognosis.

Downregulating hypoxia-inducible factor-2α improves the efficacy of doxorubicin in the treatment of hepatocellular carcinoma.

The hypoxic microenvironment inside solid tumors, including hepatocellular carcinoma (HCC), is a major cause of tumor resistance to chemotherapy. The recently identified hypoxia-inducible factor (HIF)-2 executes the hypoxia response. Its expression feature and transcriptional targets indicate a possible dominance of HIF-2 in regulating genes in HCC. The aim of the present study was to determine whether transfection of siRNA targeting HIF-2α could enhance the efficacy of doxorubicin, the most commonly used drug in the treatment of HCC. Transfection of HIF-2 siRNA into human HCC cells downregulated the expression of HIF-2α, vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-α, and cyclin D1, but had little effect on the expression of HIF-1α, fms-related tyrosine kinase-1 (Flt-1), the glucose transporter (GLUT)-1, and lactate dehydrogenase A (LDHA). Doxorubicin itself only downregulated VEGF expression. Furthermore, HIF-2 siRNA inhibited proliferation, induced cell cycle arrest at the G(0)/G(1) phase, and acted synergistically with doxorubicin to inhibit the growth of human HCC cells in vitro. Transfection of HIF-2 siRNA also downregulated tumoral expression of HIF-2α, VEGF, TGF-α, and cyclin D1 in vivo, and acted synergistically with doxorubicin to suppress the growth of HepG2 tumors established in immunodeficient mice by inhibiting cell proliferation, tumor angiogenesis and microvessel perfusion. The results of the present study suggest that targeting HIF-2α with siRNA warrants investigation as a potential strategy to enhance the efficacy of doxorubicin in the treatment of HCC.