Zhi Nie

-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.

The National Genomics Data Center (NGDC), which is a part of the China National Center for Bioinformation (CNCB), offers a comprehensive suite of database resources to support the global scientific community. Amidst the unprecedented accumulation of multi-omics data, CNCB-NGDC is committed to continually evolving and updating its core database resources through big data archiving, integrative analysis and value-added curation. Over the past year, CNCB-NGDC has expanded its collaborations with international databases and established new subcenters focusing on biodiversity, traditional Chinese medicine and tumor genetics. Substantial efforts have been made toward encompassing a broad spectrum of multi-omics data, developing innovative resources and enhancing existing resources. Notably, new resources have been developed for single-cell omics (scTWAS Atlas), genome and variation (VDGE), health and disease (CVD Atlas, CPMKG, Immunosenescence Inventory, HemAtlas, Cyclicpepedia, IDeAS), biodiversity and biosynthesis (RefMetaPlant, MASH-Ocean) and research tools (CCLHunter). All resources and services are publicly accessible at https://ngdc.cncb.ac.cn.

Triple-negative breast cancer (TNBC) is currently the most malignant subtype of breast cancers without effective targeted therapies. Mifepristone (MIF), a drug regularly used for abortion, has been reported to have anti-tumor activity in multiple hormone-dependent cancers, including luminal type breast cancers. In this study, we showed that MIF suppressed tumor growth of the TNBC cell lines and patient-derived xenografts in NOD-SCID mice. Furthermore, MIF reduced the TNBC cancer stem cell (CSC) population through down-regulating KLF5 expression, a stem cell transcription factor over-expressed in basal type TNBC and promoting cell proliferation, survival and stemness. Interestingly, MIF suppresses the expression of KLF5 through inducing the expression of miR-153. Consistently, miR-153 decreases CSC and miR-153 inhibitor rescued MIF-induced down-regulation of the KLF5 protein level and CSC ratio. Taken together, our findings suggest that MIF inhibits basal TNBC via the miR-153/KLF5 axis and MIF may be used for the treatment of TNBC.

Inorganic phosphorus (Pi) is an essential element in numerous metabolic reactions and signaling pathways, but the molecular details of these pathways remain largely unknown. In this study, metabolite profiles of maize (Zea mays L.) leaves and roots were compared between six low-Pi-sensitive lines and six low-Pi-tolerant lines under Pi-sufficient and Pi-deficient conditions to identify pathways and genes associated with the low-Pi stress response. Results showed that under Pi deprivation the concentrations of nucleic acids, organic acids and sugars were increased, but that the concentrations of phosphorylated metabolites, certain amino acids, lipid metabolites and nitrogenous compounds were decreased. The levels of secondary metabolites involved in plant immune reactions, including benzoxazinoids and flavonoids, were significantly different in plants grown under Pi-deficient conditions. Among them, the 11 most stable metabolites showed significant differences under low- and normal-Pi conditions based on the coefficient of variation (CV). Isoleucine and alanine were the most stable metabolites for the identification of Pi-sensitive and Pi-resistant maize inbred lines. With the significant correlation between morphological traits and metabolites, five low-Pi-responding consensus genes associated with morphological traits and simultaneously involved in metabolic pathways were mined by combining metabolites profiles and genome-wide association study (GWAS). The consensus genes induced by Pi deficiency in maize seedlings were also validated by reverse-transcription quantitative polymerase chain reaction (RT-qPCR). Moreover, these genes were further validated in a recombinant inbred line (RIL) population, in which the glucose-6-phosphate-1-epimerase encoding gene mediated yield and correlated traits to phosphorus availability. Together, our results provide a framework for understanding the metabolic processes underlying Pi-deficient responses and give multiple insights into improving the efficiency of Pi use in maize.

// Chunyan Wang 1, 2, 3, * , Zhi Nie 3, * , Zhongmei Zhou 1 , Hailin Zhang 1 , Rong Liu 1 , Jing Wu 1, 2, 4 , Junying Qin 1, 2 , Yun Ma 3 , Liang Chen 3 , Shumo Li 3 , Wenlin Chen 5 , Fubing Li 1, 2 , Peiguo Shi 1, 2 , Yingying Wu 3 , Jian Shen 3 , Ceshi Chen 1 1 Key Laboratory of Animal Models and Human Disease Mechanisms of The Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China 2 University of The Chinese Academy of Sciences, Beijing, China 3 First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China 4 Department of Biochemistry, Kunming Medical University, Kunming, Yunnan, China 5 Cancer Hospital, Kunming Medical University, Kunming, Yunnan, China * These authors have contributed equally to this work Correspondence to: Ceshi Chen, e-mail: chenc@mail.kiz.ac.cn Keywords: TEAD4, KLF5, p27, hippo pathway, TNBC Received: January 10, 2015      Accepted: April 10, 2015      Published: April 22, 2015 ABSTRACT Growing evidence suggests that YAP/TAZ are mediators of the Hippo pathway and promote breast cancer. However, the roles of YAP/TAZ transcription factor partners TEADs in breast cancer remain unclear. Here we found that TEAD4 was expressed in breast cancer cell lines, especially in triple negative breast cancers (TNBC) cell lines. TEAD4 binds to KLF5. Knockdown of either TEAD4 or KLF5 in HCC1937 and HCC1806 cells induced the expression of CDK inhibitor p27 . Depletion of either TEAD4 or KLF5 activated the p27 gene promoter and increased the p27 mRNA levels. Depletion of p27 partially prevents growth inhibition caused by TEAD4 and KLF5 knockdown. TEAD4 overexpression stimulated proliferation in vitro and tumor growth in mice, while stable knockdown of TEAD4 inhibited proliferation in vitro and tumor growth in mice. Thus TEAD4 and KLF5, in collaboration, promoted TNBC cell proliferation and tumor growth in part by inhibiting p27 gene transcription. TEAD4 is a potential target and biomarker for the development of novel therapeutics for breast cancer.