N6-methyladenosine (m6A) is the most prevalent, abundant and conserved internal cotranscriptional modification in eukaryotic RNAs, especially within higher eukaryotic cells. m6A modification is modified by the m6A methyltransferases, or writers, such as METTL3/14/16, RBM15/15B, ZC3H3, VIRMA, CBLL1, WTAP, and KIAA1429, and, removed by the demethylases, or erasers, including FTO and ALKBH5. It is recognized by m6A-binding proteins YTHDF1/2/3, YTHDC1/2 IGF2BP1/2/3 and HNRNPA2B1, also known as “readers”. Recent studies have shown that m6A RNA modification plays essential role in both physiological and pathological conditions, especially in the initiation and progression of different types of human cancers. In this review, we discuss how m6A RNA methylation influences both the physiological and pathological progressions of hematopoietic, central nervous and reproductive systems. We will mainly focus on recent progress in identifying the biological functions and the underlying molecular mechanisms of m6A RNA methylation, its regulators and downstream target genes, during cancer progression in above systems. We propose that m6A RNA methylation process offer potential targets for cancer therapy in the future.

BackgroundNext-generation sequencing (NGS) is an efficient and sensitive method to detect mutations from ctDNA. Many features and clinical conditions could significantly affect the concordance between ctDNA and corresponding tumor tissues. Our goal was to systematically investigate the critical factors contributing to different concordance between ctDNA and corresponding tumor tissues.MethodsWe recruited two groups of IIIB or IV lung cancer patients: The standard group to evaluate the accuracy of our method and the concordance between ctDNA and tumor tissues, and the study group with various clinical conditions. We applied our unique identification (UID) indexed capturing-based sequencing (UC-Seq) to ctDNA samples, and confirm the results by Droplet digital PCR (ddPCR).ResultsConsidering mutations detected from NGS of tumor tissues as golden standard, UC-Seq achieved overall 93.6% sensitivity for SNVs and Indels, and 0.8 Pearson correlation between tumor TMB and bTMB. Efficacious treatments, long sampling date (more than 2 weeks) between tumor tissues and ctDNA and low concentrations of cfDNA (less than 9 ng/ml) could significantly decrease the concordance between ctDNA and tumor tissues. About 84% mutations showed shorter mutant fragment length than that of wild-type fragments, and the AFs of mutations could be significantly enriched in small-size ctDNA.ConclusionsIn late-stage lung cancer patients, ctDNA generally has high concordance with tumor tissues. However it could be significantly affected by three clinical conditions which could dynamically change the content of ctDNA. Moreover, the detection limit could be further extended by enriching small-size ctDNA in the preparation of samples.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4199-7) contains supplementary material, which is available to authorized users.

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Background Non-small cell lung cancer (NSCLC) is the most common type of human lung cancers, which has diverse pathological features. Although many signaling pathways and therapeutic targets have been defined to play important roles in NSCLC, limiting efficacies have been achieved. Methods Bioinformatics methods were used to identify differential long non-coding RNA expression in NSCLC. Real-time RT-PCR experiments were used to examine the expression pattern of lncRNA PKMYT1AR, miR-485-5p. Both in vitro and in vivo functional assays were performed to investigate the functional role of PKMYT1AR/miR-485-5p/PKMYT1 axis on regulating cell proliferation, migration and tumor growth. Dual luciferase reporter assay, fluorescent in situ hybridization (FISH), immunoblot, co-immunoprecipitation experiments were used to verify the molecular mechanism. Result Here, we identify a human-specific long non-coding RNA (lncRNA, ENST00000595422), termed PKMYT1AR (PKMYT1 associated lncRNA), that is induced in NSCLC by Yin Yang 1 (YY1) factor, especially in cancerous cell lines (H358, H1975, H1299, H1650, A549 and SPC-A1) compared to that in normal human bronchial epithelium cell line (BEAS-2B). We show that PKMYT1AR high expression correlates with worse clinical outcome, and knockdown of PKMYT1AR inhibits tumor cell proliferation, migration and xenograft tumor formation abilities. Bioinformatic analysis and a luciferase assay demonstrate that PKMYT1AR directly interacts with miR-485-5p to attenuate the inhibitory role on its downstream oncogenic factor PKMYT1 (the protein kinase, membrane-associated tyrosine/threonine 1) in NSCLC. Furthermore, we uncover that miR-485-5p is downregulated in both cancerous cell lines and peripheral blood serum isolated from NSCLC patients compared to reciprocal control groups. Consistently, forced expression of miR-485-5p inhibits the proliferation and migration abilities of tumor cells. Moreover, we provide evidence showing that PKMYT1AR targeting antisense oligonucleotide (ASO) dramatically inhibit tumor growth in vivo. Mechanistic study shows that PKMYT1AR/ miR-485-5p /PKMYT1 axis promotes cancer stem cells (CSCs) maintenance in NSCLC via inhibiting β-TrCP1 mediated ubiquitin degradation of β-catenin proteins, which in turn causes enhanced tumorigenesis. Conclusions Our findings reveal the critical role of PKMYT1AR/miR-485-5p /PKMYT1 axis during NSCLC progression, which could be used as novel therapeutic targets in the future.