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Paeonia lactiflora Pall. (Paeonia) has aroused many concerns due to its extensive medicinal value, in which monoterpene glucoside paeoniflorin and its derivatives are the active chemical components. However, little is known in the molecular mechanism of monoterpenoids biosynthesis, and the regulation network between small RNAs and mRNAs in monoterpenoids biosynthesis has not been investigated yet. Herein, we attempted to reveal the tissue-specific regulation network of miRNAs and their targets related to paeoniaflorin and monoterpenoids biosynthesis in Paeonia by combining mRNA and miRNA expression data with degradome analysis. In all, 289 miRNAs and 30177 unigenes were identified, of which nine miRNAs from seven miRNA families including miR396, miR393, miR835, miR1144, miR3638, miR5794 and miR9555 were verified as monoterpenoids biosynthesis-related miRNAs by degradome sequencing. Moreover, the co-expression network analysis showed that four monoterpenoids-regulating TFs, namely AP2, MYBC1, SPL12 and TCP2, were putatively regulated by five miRNAs including miR172, miR828, miR858, miR156 and miR319, respectively. The present study will improve our knowledge of the molecular mechanisms of the paeoniaflorin and monoterpenoids biosynthesis mediated by miRNA to a new level, and provide a valuable resource for further study on Paeonia.

Chemoresistance remains a major obstacle to effective treatment in patients with ovarian cancer, and recently increasing evidences suggest that miRNAs are involved in drug-resistance. In this study, we investigated the role of miRNAs in regulating cisplatin resistance in ovarian cancer cell line and analyzed their possible mechanisms. We profiled miRNAs differentially expressed in cisplatin-resistant human ovarian cancer cell line A2780/DDP compared with parental A2780 cells using microarray. Four abnormally expressed miRNAs were selected (miR-146a,-130a, -374a and miR-182) for further studies. Their expression were verified by qRT-PCR. MiRNA mimics or inhibitor were transfected into A2780 and A2780/DDP cells and then drug sensitivity was analyzed by MTS array. RT-PCR and Western blot were carried out to examine the alteration of MDR1, PTEN gene expression. A total of 32 miRNAs were found to be differentially expressed in A2780/DDP cells. Among them, miR-146a was down-regulated and miR-130a,-374a,-182 were upregulated in A2780/DDP cells, which was verified by RT-PCR. MiR-130a and miR-374a mimics decreased the sensitivity of A2780 cells to cisplatin, reversely, their inhibitors could resensitize A2780/DDP cells. Furthermore, overexpression of miR-130a could increase the MDR1 mRNA and P-gp levels in A2780 and A2780/DDP cells, whereas knockdown of miR-130a could inhibit MDR1 gene expression and upregulate the PTEN protein expression .In a conclusion, the deregulation of miR-374a and miR-130a may be involved in the development and regulation of cisplatin resistance in ovarian cancer cells. This role of miR-130a may be achieved by regulating the MDR1 and PTEN gene expression.