AIM  To investigate the expression and significance of miR-206 in pulmonary hypertension.

  METHODS  Rat model of pulmonary hypertension was established. After 1, 7, 14, 21 and 28 days of hypoxia exposure, the right lower lobe tissue and peripheral blood of the rats were extracted. The expression of miR-206 was detected by real-time quantitative PCR. The primary PASMC was isolated, miR-206 mimics transfected were exposed to hypoxia and cell proliferation was detected. By bioinformatics analysis, hypoxia-inducible factor-1α (HIF-1α) was selected as a candidate gene for miR-206 and dual luciferase reporter assay was used to verify whether miR-206 could directly regulate HIF-1α. After co-transfection with miR-206mimics and HIF-1α over-expression plasmid, the proliferation of PASMC cells was detected.

  RESULTS  The expression of miR-206 in rat lung tissue decreased after hypoxia exposure (P < 0.05) and serum miR-206 was also significantly decreased (P < 0.05). The expression of miR-206 in isolated cultured PASMC was significantly decreased (P < 0.05) and the proliferation of PASMC was significantly increased when miR-206 was lowly expressed (P < 0.05). The transfection of miR-206 mimics could antagonize the proliferation of PASMC induced by hypoxia exposure (P < 0.05). Bioinformatics found that the 3' untranslated region (3'UTR) of HIF-1α had a binding site for miR-206. In the luciferase report, the gene activity of PASMC co-transfected with miR-206 and HIF-1α (wild type 3'UTR) was significantly down-regulated (P < 0.05). After co-transfection of miR-206 mimics, the cell proliferation induced by up-regulation of HIF-1α was reversed (P < 0.05).

  CONCLUSION  Hypoxia-induced down-regulation of miR-206 promotes PH by targeting the HIF-1α pathway in PASMC and miR-206 may be a trigger for hypoxia-induced PH early stage.