Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related deaths worldwide. YTHDF2 is a reader of N6-methyladenosine (m6A) on RNA and plays a critical role in the initiation and propagation of myeloid leukemia; however, whether YTHDF2 controls the development of LUAD remains to be explored. Here, we found that YTHDF2 was significantly upregulated in LUAD compared with paracancerous normal tissues, and YTHDF2 knockdown drastically inhibited, while its overexpression promoted, cell growth, colony formation and migration of LUAD cells in vitro. In addition, YTHDF2 knockdown significantly inhibited tumorigenesis in a murine tumor xenograft model. Through the integrative analysis of RNA-seq, m6A-seq, CLIP-seq, and RIP-seq datasets, we identified a set of potential direct targets of YTHDF2 in LUAD, among which we confirmed AXIN1, which encodes a negative regulator of the Wnt/β-catenin signaling, as a direct target of YTHDF2. YTHDF2 promoted AXIN1 mRNA decay and subsequently activated the Wnt/β-catenin signaling. Knockout of AXIN1 sufficiently rescued the inhibitory effect of YTHDF2 depletion on lung cancer cell proliferation, colony-formation, and migration. These results revealed YTHDF2 to be a contributor of LUAD development acting through the upregulation of the AXIN1/Wnt/β-catenin signaling, which can be a potential therapeutic target for LUAD.

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Platelet-rich plasma (PRP) has seen wide clinical use owing to its regenerative and repair abilities. Objective: To investigate the anti-photoaging effects of pre-and post-treatment of PRP on UVB-damaged HaCaT cells. Methods: HaCaT cells were irradiated with 80 mJ/cm 2 UVB, before or after PRP treatment (1000 × 10 7 /L), and following measurements were taken: survival rate of UVB-irradiated HaCaT cells, malondialdehyde (MDA) content and activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT). Western blot was used to determine the effect of different PRP intervention on the expression of PI3K, AKT, ERK, MMP-1, MMP-9, TIMP-1 and γ-H2AX in the UVB-irradiated HaCaT cells. Results: pre-and post-PRP treatment reduced MDA content and increased the activities of GSH-Px, SOD and CAT in photoaged HaCaT cells. These changes resulted in reduced cytotoxic effects. Besides, different PRP intervention promoted cell proliferation via PI3K/AKT pathway. Furthermore, PRP application suppressed the expression of γ-H2AX. Also, PRP intervention alleviated photoaging effects by upregulating the expression level of tissue inhibitor of metalloproteinases-1 (TIMP-1) while downregulating matrix metalloproteinase (MMP) expression level in photoaged HaCaT cells. Conclusion: pre-and post-PRP treatment play anti-photoaging role through strengthening cellular oxidative defense capacity, mitigating MMP expression, alleviating DNA damages and promoting proliferation of UVB-irradiated HaCaT cells.Abbreviations: APB-PRP, adult peripheral blood-derived PRP; HaCaT, human keratinocyte cells; PRP, platelet-rich plasma; UCB-PRP, umbilical cord blood-derived PRP.

BackgroundThe Pacific abalone, Haliotis discus hannai, is the most important cultivated abalone in China. Improving abalone muscle growth and increasing the rate of growth are important genetic improvement programs in this industry. MicroRNAs are important small noncoding RNA molecules that regulate post-transcription gene expression. However, no miRNAs have been reported to regulate muscle growth in H. discus hannai.Resultswe profiled six small RNA libraries for three large abalone individuals (L_HD group) and three small individuals (S_HD group) using RNA sequencing technology. A total of 205 miRNAs, including 200 novel and 5 known miRNAs, were identified. In the L_HD group, 3 miRNAs were up-regulated and 7 were down-regulated compared to the S_HD specimens. Bioinformatics analysis of miRNA target genes revealed that miRNAs participated in the regulation of cellular metabolic processes, the regulation of biological processes, the Wnt signaling pathway, ECM-receptor interaction, and the MAPK signaling pathway, which are associated with regulating growth. Bone morphogenetic protein 7 (BMP7) was verified as a target gene of hdh-miR-1984 by a luciferase reporter assay and we examined the expression pattern in different developmental stages.ConclusionThis is the first study to demonstrate that miRNAs are related to the muscle growth of H. discus hannai. This information could be used to study the mechanisms of abalone muscle growth. These DE-miRNAs may be useful as molecular markers for functional genomics and breeding research in abalone and closely related species.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-5347-9) contains supplementary material, which is available to authorized users.

Myostatin, also known as GDF8, is a member of the transforming growth factor-β (TGF-β) superfamily. In vertebrates, myostatin negatively regulates the growth of skeletal muscle. In invertebrates, it has been reported to be closely related to animal growth. However, knowledge concerning the molecular mechanisms involved in the myostatin regulation of molluscan growth is limited. In this study, we found that the hdh-myostatin open reading frame (ORF) comprised 1470 base pairs that encoded 489 amino acids and contained structural characteristics typical of the TGF-β superfamily, including a C-terminal signal peptide, a propeptide domain, and TGF-β region. Gene expression analysis revealed that hdh-myostatin mRNA was widely expressed at different levels in all of the examined tissues of Haliotis discus hannai. Nine single nucleotide polymorphisms (SNPs) were associated with the growth traits. RNA interference (RNAi) against hdh-myostatin mRNA significantly downregulated hdh-myostatin at days 1, 15, and 30 post injection, and the pattern was correlated with downregulation of the genes TGF-β receptor type-I (hdh-TβR I), activin receptor type-IIB (hdh-ActR IIB), and mothers against decapentaplegic 3 (hdh-Smad3). After one month of the RNAi experiment, the shell lengths and total weights increased in the abalone, Haliotis discus hannai. The results of qRT-PCR showed that the hdh-myostatin mRNA level was higher in the slow-growing group than in the fast-growing group. These results suggest that hdh-myostatin is involved in the regulation of growth, and that these SNPs would be informative for further studies on selective breeding in abalone.