Background Colorectal carcinoma (CRC) is one of the most common malignant tumors, and its main cause of death is tumor metastasis. RNA N 6 -methyladenosine (m 6 A) is an emerging regulatory mechanism for gene expression and methyltransferase-like 3 (METTL3) participates in tumor progression in several cancer types. However, its role in CRC remains unexplored. Methods Western blot, quantitative real-time PCR (RT-qPCR) and immunohistochemical (IHC) were used to detect METTL3 expression in cell lines and patient tissues. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and transcriptomic RNA sequencing (RNA-seq) were used to screen the target genes of METTL3. The biological functions of METTL3 were investigated in vitro and in vivo. RNA pull-down and RNA immunoprecipitation assays were conducted to explore the specific binding of target genes. RNA stability assay was used to detect the half-lives of the downstream genes of METTL3. Results Using TCGA database, higher METTL3 expression was found in CRC metastatic tissues and was associated with a poor prognosis. MeRIP-seq revealed that SRY (sex determining region Y)-box 2 (SOX2) was the downstream gene of METTL3. METTL3 knockdown in CRC cells drastically inhibited cell self-renewal, stem cell frequency and migration in vitro and suppressed CRC tumorigenesis and metastasis in both cell-based models and PDX models. Mechanistically, methylated SOX2 transcripts, specifically the coding sequence (CDS) regions, were subsequently recognized by the specific m 6 A “reader”, insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2), to prevent SOX2 mRNA degradation. Further, SOX2 expression positively correlated with METTL3 and IGF2BP2 in CRC tissues. The combined IHC panel, including “writer”, “reader”, and “target”, exhibited a better prognostic value for CRC patients than any of these components individually. Conclusions Overall, our study revealed that METTL3, acting as an oncogene, maintained SOX2 expression through an m 6 A-IGF2BP2-dependent mechanism in CRC cells, and indicated a potential biomarker panel for prognostic prediction in CRC. Electronic supplementary material The online version of this article (10.1186/s12943-019-1038-7) contains supplementary material, which is available to authorized users.

Hypoxia occurs naturally at high-altitudes and pathologically in hypoxic solid tumors. Here, we report that genes involved in various human cancers evolved rapidly in Tibetans and six Tibetan domestic mammals compared to reciprocal lowlanders. Furthermore, m6A modified mRNA binding protein YTHDF1, one of evolutionary positively selected genes for high-altitude adaptation is amplified in various cancers, including non-small cell lung cancer (NSCLC). We show that YTHDF1 deficiency inhibits NSCLC cell proliferation and xenograft tumor formation through regulating the translational efficiency of CDK2, CDK4, and cyclin D1, and that YTHDF1 depletion restrains de novo lung adenocarcinomas (ADC) progression. However, we observe that YTHDF1 high expression correlates with better clinical outcome, with its depletion rendering cancerous cells resistant to cisplatin (DDP) treatment. Mechanistic studies identified the Keap1-Nrf2-AKR1C1 axis as the downstream mediator of YTHDF1. Together, these findings highlight the critical role of YTHDF1 in both hypoxia adaptation and pathogenesis of NSCLC.

Selective reduction of ketone/aldehydes to alcohols is of great importance in green chemistry and chemical engineering. Highly efficient catalysts are still demanded to work under mild conditions, especially at room temperature. Here we present a synergistic function of singleatom palladium (Pd 1 ) and nanoparticles (Pd NPs ) on TiO 2 for highly efficient ketone/aldehydes hydrogenation to alcohols at room temperature. Compared to simple but inferior Pd 1 /TiO 2 and Pd NPs /TiO 2 catalysts, more than twice activity enhancement is achieved with the Pd 1+NPs /TiO 2 catalyst that integrates both Pd 1 and Pd NPs on mesoporous TiO 2 supports, obtained by a simple but large-scaled spray pyrolysis route. The synergistic function of Pd 1 and Pd NPs is assigned so that the partial Pd 1 dispersion contributes enough sites for the activation of C=O group while Pd NPs site boosts the dissociation of H 2 molecules to H atoms. This work not only contributes a superior catalyst for ketone/aldehydes hydrogenation, but also deepens the knowledge on their hydrogenation mechanism and guides people to engineer the catalytic behaviors as needed.

N6-methyladenosine (m6A) is the most abundant posttranscriptional modification in mammalian mRNA molecules and has a crucial function in the regulation of many fundamental biological processes. The m6A modification is a dynamic and reversible process regulated by a series of writers, erasers and readers (WERs). Different WERs might have different functions, and even the same WER might function differently in different conditions, which are mostly due to different downstream genes being targeted by the WERs. Therefore, identification of the targets of WERs is particularly important for elucidating this dynamic modification. However, there is still no public repository to host the known targets of WERs. Therefore, we developed the m6A WER target gene database (m6A2Target) to provide a comprehensive resource of the targets of m6A WERs. M6A2Target provides a user-friendly interface to present WER targets in two different modules: ‘Validated Targets’, referred to as WER targets identified from low-throughput studies, and ‘Potential Targets’, including WER targets analyzed from high-throughput studies. Compared to other existing m6A-associated databases, m6A2Target is the first specific resource for m6A WER target genes. M6A2Target is freely accessible at http://m6a2target.canceromics.org.

Hyperpolarization techniques based on the use of para-hydrogen provide orders of magnitude signal enhancement for magnetic resonance spectroscopy and imaging. The main drawback limiting widespread applicability of para-hydrogen-based techniques in biomedicine is the presence of organometallic compounds (the polarization transfer catalysts) in solution with hyperpolarized contrast agents. These catalysts are typically complexes of platinum-group metals, and their administration in vivo should be avoided. Herein, we show how extraction of a hyperpolarized compound from an organic phase to an aqueous phase combined with a rapid (less than 10 s) Ir-based catalyst capture by metal scavenging agents can produce pure para-hydrogen-based hyperpolarized contrast agents, as demonstrated by high-resolution nuclear magnetic resonance (NMR) spectroscopy and inductively coupled plasma atomic emission spectroscopy (ICP-AES). The presented methodology enables fast and efficient means of producing pure hyperpolarized aqueous solutions for biomedical and other uses.