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Cryptotanshinone suppresses key onco-proliferative and drugresistant pathways of chronic myeloid leukemia by targeting STAT5 and STAT3 phosphorylation

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Science china(Life Sciences) 2018年第9期61卷 999-1009页

作者： Bowen Dong Zirui Liang Zhirong Chen Bin Li lingling zheng Jianhua Yang Hui Zhou {2. qu key laboratory of {2. engineering of the ministry of education State Key Laboratory for Biocontrol Sun Yat-sen University

C-Myc and signal transducer and activator of transcription(STAT) family proteins have been proposed to be important downstream genes of BCR-ABL, which characterizes most cases of chronic myeloid leukemia(CML). Here, we report a c-Myc pathway-targeted screening of seven natural anticancer compounds, in which we identified cryptotanshinone as a highly promising agent for CML therapy. Cryptotanshinone depletes c-Myc in CML by repressing the phosphorylation of *** viability of K562.cells correlated with p-STAT5 suppression. Unexpectedly, imatinib activates rather than inhibits the phosphorylation of STAT3 in K562.cells. We demonstrated that cryptotanshinone, as a dual inhibitor of p-STAT5 and p-STAT3,can effectively block IL-6-mediated STAT3 activation and reverse BCR-ABL kinase-independent drug resistance. Moreover, we showed that the epigenetic rebalance between decreased BCR-ABL/STAT5/c-Myc and enhanced STAT3/multi-drug resistance(MDR) pathways is characteristic of the cancer stem cell-like property of K562.ADR. Simultaneously suppressing these two pathways using cryptotanshinone proves to be critical for the malignant network redress and MDR reversal of K562.ADR. These studies reveal the dual functions of cryptotanshinone that suppress {2. oncogenic proliferation and drug-resistant pathways in CML cells by targeting p-STAT5 and p-STAT3, providing a new strategy for CML therapy that takes advantage of natural products.

关键词： p-STAT3/5 microRNA CML MDR

Applications of RNA Indexes for Precision Oncology in Breast Cancer

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Genomics, Proteomics & Bioinformatics 2018年第2期16卷 108-119页

作者： Liming Ma Zirui Liang Hui Zhou lianghu qu key laboratory of {2. engineering of the ministry of education State Key Laboratory of Biocontrol School of Life SciencesSun Yat-sen University

Precision oncology aims to offer the most appropriate treatments to cancer patients mainly based on their individual genetic information. Genomics has provided numerous valuable data on driver mutations and risk loci; however, it remains a formidable challenge to transform these data into therapeutic agents. Transcriptomics describes the multifarious expression patterns of both mRNAs and non-coding RNAs （ncRNAs）, which facilitates the deciphering of genomic codes. In this review, we take breast cancer as an example to demonstrate the applications of these rich RNA resources in precision medicine exploration. These include the use of mRNA profiles in triple-negative breast cancer （TNBC） subtyping to inform corresponding candidate targeted therapies; current advancements and achievements of high-throughput RNA interference （RNAi） screening technologies in breast cancer; and microRNAs as functional signatures for defining cell identities and regulating the biological activities of breast cancer cells. We summarize the benefits of transcriptomic analyses in breast cancer management and propose that unscrambling the core signaling networks of cancer may be an important task of multiple-omic data integration for precision oncology.

关键词： Precision oncology Transcriptomics RNA interference microRNA Breast cancer

CLIP: viewing the RNA world from an RNA-protein interactome perspective

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Science china(Life Sciences) 2015年第1期58卷 75-88页

作者： ZHANG Yin XIE ShuJuan XU Hui qu lianghu key laboratory of {2. engineering of ministry of education State Key Laboratory for BiocontrolSun Yat-Sen University

The pervasive transcription of the genome creates many types of non-coding RNAs(nc RNAs).However,we know very little regarding the functions and the regulatory mechanisms of these nc *** the interactions of RNA and RNA binding proteins(RBPs) is vital because it can allow us to truly understand how these nc RNAs behave in ***-throughput sequencing of RNA isolated by cross-linking immunoprecipitation(HITS-CLIP or CLIP-seq) and its variants have been successfully used as systemic techniques to study RBP binding *** this review,we will explain the major differences between the CLIP techniques,summarize successful applications of these techniques,discuss limitations of CLIP,present some suggested solutions and project their promising future roles in studying the RNA world.

关键词： CLIP CLASH RPBs nc RNAs functional RNomics

Identification of three novel noncoding RNAs from Drosophila melanogaster

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Chinese Science Bulletin 2006年第22期51卷 2737-2742页

作者： HE Hualiang ZHOU Hui XIAO Zhendong ZENG Xianfen CHEN Junyu zheng Tao qu {2. key laboratory of {2. engineering of the ministry of education State Key Laboratory for Biocontrol Sun Yat-sen University Guangzhou 510275 China

三新奇小非编码的 RNA 从 D 的保存 intronicregions 被识别。由使用比较基因组学方法和分子的生物学途径的 melanogaster。Oneis 以一个 combinated 方法的新奇 snoRNA，它 snoRNAfamily 显示典型地代表 C/D 盒子的结构的特征并且为在 ... 详细信息

三新奇小非编码的 RNA 从 D 的保存 intronicregions 被识别。由使用比较基因组学方法和分子的生物学途径的 melanogaster。Oneis 以一个 combinated 方法的新奇 snoRNA，它 snoRNAfamily 显示典型地代表 C/D 盒子的结构的特征并且为在 C2.73 指导 *** 2.S rRNA 的 2.'-O-methylation 拥有一个 10-nt-long rRNA 反感觉元素。另外的二是预言先锋采用已知的 miRNA 的 astem 环结构特征的 miRNAs。二 miRNAs 基因看起来有无所不在的表示侧面， ~ 2.-nt RNA 抄本由北弄污检测了。我们的学习 revealed396 多种类 intronic 保存了与长度 from100 在 introns 嵌套到 500 bp 的序列(MCIS ) 。除了编码的小 RNA， MCIS 可能作为涉及基因抄写或 post-transcriptional 处理的 c/s-acting 元素工作。

关键词：果蝇 miRNA MCIS 分子生物学

A Helm model for microRNA regulation in cell fate decision and conversion

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Science china(Life Sciences) 2013年第10期56卷 897-906页

作者： XIE ShuJuan ZHANG Yin qu lianghu XU Hui key laboratory of {2. engineering of ministry of education State Key Laboratory for BiocontrolSun Yat-sen University

microRNAs （miRNAs） constitute a unique class of endogenous small non-coding RNAs that regulate gene expression post-transcriptionally. Studies over the past decade have uncovered a r^curring paradigm in which miRNAs are {2. regulators of cellular behavior under various physiological and pathological conditions. Most surprising is the recent observation that miRNAs have emerged as competent players in somatic cell reprogramming, suggesting an especially significant role for these small RNAs in cell fate settings. Here, we discuss the possible mechanisms underlying miRNA-mediated cell programming （i.e., the development and differentiation of embryonic stem cells） and reprogramming （i.e., turning somatic cells into pluripo- tent stem cells or other lineages）, and provide a ＂Helm＂ model of miRNAs in cell fate decision and conversion.

关键词： miRNA(s) cell fate development differentiation embryonic stem cells reprogramming iPS transdifferentiation

The Function of MicroRNAs in Renal Development and Pathophysiology

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Journal of genetics and Genomics 2013年第4期40卷 143-152页

作者： Liming Ma lianghu qu key laboratory of {2. engineering of the ministry of education State Key Laboratory for BiocontrolSun Yat-sen University

MicroRNAs（miRNAs） are a class of endogenous small non-coding RNAs that modulate diverse biological processes predominantly by translation inhibition or induction of mRNA *** are important regulatory elements involved in renal physiology and *** of miRNAs disrupts early kidney development,renal progenitor cell differentiation and the maintenance of mature *** are also reported to participate in various renal diseases,including chronic kidney disease,acute kidney injury, allograft acute rejection and renal cell *** regulated miRNAs may represent innovative biomarkers for diagnosis and ***,determining the roles of miRNAs in different types of renal diseases will help to clarify the pathogenesis and facilitate the development of novel therapies.

关键词： MicroRNA Renal development Renal pathophysiology