N 6 -Methyladenosine (m 6 A) RNA modification brings a new dawn for RNA modification researches in recent years. This posttranscriptional RNA modification is dynamic and reversible, and is regulated by methylases (“writers”), demethylases (“erasers”), and proteins that preferentially recognize m 6 A modifications (“readers”). The change of RNA m 6 A modification regulates RNA metabolism in eucaryon, including translation, splicing, exporting, decay, and processing. Thereby the dysregulation of m 6 A may lead to tumorigenesis and progression. Given the tumorigenic role of abnormal m 6 A expression, m 6 A regulators may function as potential clinical therapeutic targets for cancers. In this review, we emphasize on the underlying mechanisms of m 6 A modifications in tumorigenesis and further introduce the potential m 6 A regulators-associated therapeutic targets for tumor therapy.

BackgroundMicroRNAs are regulators that can play an essential role in tumorigenesis. Although miR-302 families have been suggested to be tumor repressors in human cancer, the mechanism by which they suppress tumor development remains to be defined. In this study, we discover that miR302b suppresses tumor proliferation may due to directly targeting EGFR in human hepatocellular carcinoma (HCC).MethodsQRT-PCR was used to assess miR-302b and EGFR expression in 27 pairs of clinical hepatocellular carcinoma tissues and their corresponding adjacent nontumorous liver tissues. MTT, colony formation, immunofluorescence staining, and cell cycle assays were used to examine the tumor suppressor role of miR302b in cell proliferation. Luciferase assays were performed to assess the EGFR was a novel target of miR-302b. Western blot assay was used to validate the protein expression level.ResultsWe demonstrated that miR-302b was frequently down-regulated, whereas EGFR was up-regulated in 27 pairs of clinical HCC and non-tumorous counterparts. The dual-luciferase reporter assays revealed that EGFR was a novel target of miR-302b. Re-expression of miR-302b resulted in the inhibition of proliferation in hepatocellular carcinoma SMMC-7721 cells. The silencing of EGFR by miR-302b or siEGFR led to down-regulation of proliferation-related proteins, such as AKT2, CCND1, and CDK2.ConclusionmiR-302b suppresses HCC growth may due to targeting the EGFR/AKT2/CCND1 pathway.

No abstract

Dear Editor, Genome editing has found applications in almost every field in biology and medicine and has permeated many aspects of our society. In particular, the clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated nuclease 9 (Cas9) system-has been widely used in genome editing because of its convenience, simplicity, efficiency, and low cost. It is generally thought that Cas9 cleavage generates blunt-ended double-strand breaks (DSBs) at the 3 base pairs upstream (−3 bp) of protospacer adjacent motif (PAM). In addition, the editing outcomes resulted from several competing cellular DSB repair pathways such as canonical or classic nonhomologous end joining (cNHEJ) and microhomologymediated end joining (MMEJ) are random, imprecise, and unpredictable. Only homologous recombination with a donor template (HDR, homology directed repair) is thought to be precise. However, recent studies revealed that the CRISPR-Cas9 genome editing system is precise and predictable even without donor templates for natural or synthetic targeting sites 1-6. Specifically, it is firmly established that Cas9-mediated 1-bp insertions are predictable 1-3,7-9 because they are resulted from ligation and polymerase-fill-in of DSB ends with 1-bp overhang from