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Xianzhi Lin

Assistant Professor of Biology at Duke Kunshan University
DKU Faculty

Selected Publications


Fallopian tube single cell analysis reveals myeloid cell alterations in high-grade serous ovarian cancer.

Journal Article iScience · March 2024 Most high-grade serous ovarian cancers (HGSCs) likely initiate from fallopian tube (FT) epithelia. While epithelial subtypes have been characterized using single-cell RNA-sequencing (scRNA-Seq), heterogeneity of other compartments and their involvement in ... Full text Cite

A biallelic multiple nucleotide length polymorphism explains functional causality at 5p15.33 prostate cancer risk locus.

Journal Article Nature communications · August 2023 To date, single-nucleotide polymorphisms (SNPs) have been the most intensively investigated class of polymorphisms in genome wide associations studies (GWAS), however, other classes such as insertion-deletion or multiple nucleotide length polymorphism (MNL ... Full text Cite

Single-cell transcriptomic analysis of endometriosis.

Journal Article Nature genetics · February 2023 Endometriosis is a common condition in women that causes chronic pain and infertility and is associated with an elevated risk of ovarian cancer. We profiled transcriptomes of >370,000 individual cells from endometriomas (n = 8), endometriosis (n = 28), eut ... Full text Cite

circCsnk1g3- and circAnkib1-regulated interferon responses in sarcoma promote tumorigenesis by shaping the immune microenvironment.

Journal Article Nature communications · November 2022 Exonic circular RNAs (circRNAs) produce predominantly non-coding RNA species that have been recently profiled in many tumors. However, their functional contribution to cancer progression is still poorly understood. Here, we identify the circRNAs expressed ... Full text Cite

In vivo discovery of RNA proximal proteins via proximity-dependent biotinylation.

Journal Article RNA biology · December 2021 RNA molecules function as messenger RNAs (mRNAs) that encode proteins and noncoding transcripts that serve as adaptor molecules, structural components, and regulators of genome organization and gene expression. Their function and regulation are largely med ... Full text Cite

Predicting master transcription factors from pan-cancer expression data.

Journal Article Science advances · November 2021 Critical developmental “master transcription factors” (MTFs) can be subverted during tumorigenesis to control oncogenic transcriptional programs. Current approaches to identifying MTFs rely on ChIP-seq data, which is unavailable for many cancers. We develo ... Full text Cite

Single-cell transcriptomics identifies gene expression networks driving differentiation and tumorigenesis in the human fallopian tube.

Journal Article Cell reports · April 2021 The human fallopian tube harbors the cell of origin for the majority of high-grade serous "ovarian" cancers (HGSCs), but its cellular composition, particularly the epithelial component, is poorly characterized. We perform single-cell transcriptomic profili ... Full text Cite

Non-coding somatic mutations converge on the PAX8 pathway in ovarian cancer.

Journal Article Nature communications · April 2020 The functional consequences of somatic non-coding mutations in ovarian cancer (OC) are unknown. To identify regulatory elements (RE) and genes perturbed by acquired non-coding variants, here we establish epigenomic and transcriptomic landscapes of primary ... Full text Cite

Super-Enhancer-Associated LncRNA UCA1 Interacts Directly with AMOT to Activate YAP Target Genes in Epithelial Ovarian Cancer.

Journal Article iScience · July 2019 Long noncoding RNAs (lncRNAs) have emerged as critical regulators of tumorigenesis, and yet their mechanistic roles remain challenging to characterize. Here, we integrate functional proteomics with lncRNA-interactome profiling to characterize Urothelial Ca ... Full text Cite

A transcriptome-wide association study of high-grade serous epithelial ovarian cancer identifies new susceptibility genes and splice variants.

Journal Article Nature genetics · May 2019 We sought to identify susceptibility genes for high-grade serous ovarian cancer (HGSOC) by performing a transcriptome-wide association study of gene expression and splice junction usage in HGSOC-relevant tissue types (N = 2,169) and the largest genome-wide ... Full text Cite

RNA editing in nascent RNA affects pre-mRNA splicing.

Journal Article Genome research · June 2018 In eukaryotes, nascent RNA transcripts undergo an intricate series of RNA processing steps to achieve mRNA maturation. RNA editing and alternative splicing are two major RNA processing steps that can introduce significant modifications to the final gene pr ... Full text Cite

Optimizing exosomal RNA isolation for RNA-Seq analyses of archival sera specimens.

Journal Article PloS one · January 2018 Exosomes are endosome-derived membrane vesicles that contain proteins, lipids, and nucleic acids. The exosomal transcriptome mediates intercellular communication, and represents an understudied reservoir of novel biomarkers for human diseases. Next-generat ... Full text Cite

Global analyses of endonucleolytic cleavage in mammals reveal expanded repertoires of cleavage-inducing small RNAs and their targets.

Journal Article Nucleic acids research · April 2016 In mammals, small RNAs are important players in post-transcriptional gene regulation. While their roles in mRNA destabilization and translational repression are well appreciated, their involvement in endonucleolytic cleavage of target RNAs is poorly unders ... Full text Cite

Alternative splicing modulated by genetic variants demonstrates accelerated evolution regulated by highly conserved proteins.

Journal Article Genome research · April 2016 Identification of functional genetic variants and elucidation of their regulatory mechanisms represent significant challenges of the post-genomic era. A poorly understood topic is the involvement of genetic variants in mediating post-transcriptional RNA pr ... Full text Cite

Fallopian tube single cell analysis reveals myeloid cell alterations in high-grade serous ovarian cancer.

Journal Article iScience · March 2024 Most high-grade serous ovarian cancers (HGSCs) likely initiate from fallopian tube (FT) epithelia. While epithelial subtypes have been characterized using single-cell RNA-sequencing (scRNA-Seq), heterogeneity of other compartments and their involvement in ... Full text Cite

A biallelic multiple nucleotide length polymorphism explains functional causality at 5p15.33 prostate cancer risk locus.

Journal Article Nature communications · August 2023 To date, single-nucleotide polymorphisms (SNPs) have been the most intensively investigated class of polymorphisms in genome wide associations studies (GWAS), however, other classes such as insertion-deletion or multiple nucleotide length polymorphism (MNL ... Full text Cite

Single-cell transcriptomic analysis of endometriosis.

Journal Article Nature genetics · February 2023 Endometriosis is a common condition in women that causes chronic pain and infertility and is associated with an elevated risk of ovarian cancer. We profiled transcriptomes of >370,000 individual cells from endometriomas (n = 8), endometriosis (n = 28), eut ... Full text Cite

circCsnk1g3- and circAnkib1-regulated interferon responses in sarcoma promote tumorigenesis by shaping the immune microenvironment.

Journal Article Nature communications · November 2022 Exonic circular RNAs (circRNAs) produce predominantly non-coding RNA species that have been recently profiled in many tumors. However, their functional contribution to cancer progression is still poorly understood. Here, we identify the circRNAs expressed ... Full text Cite

In vivo discovery of RNA proximal proteins via proximity-dependent biotinylation.

Journal Article RNA biology · December 2021 RNA molecules function as messenger RNAs (mRNAs) that encode proteins and noncoding transcripts that serve as adaptor molecules, structural components, and regulators of genome organization and gene expression. Their function and regulation are largely med ... Full text Cite

Predicting master transcription factors from pan-cancer expression data.

Journal Article Science advances · November 2021 Critical developmental “master transcription factors” (MTFs) can be subverted during tumorigenesis to control oncogenic transcriptional programs. Current approaches to identifying MTFs rely on ChIP-seq data, which is unavailable for many cancers. We develo ... Full text Cite

Single-cell transcriptomics identifies gene expression networks driving differentiation and tumorigenesis in the human fallopian tube.

Journal Article Cell reports · April 2021 The human fallopian tube harbors the cell of origin for the majority of high-grade serous "ovarian" cancers (HGSCs), but its cellular composition, particularly the epithelial component, is poorly characterized. We perform single-cell transcriptomic profili ... Full text Cite

Non-coding somatic mutations converge on the PAX8 pathway in ovarian cancer.

Journal Article Nature communications · April 2020 The functional consequences of somatic non-coding mutations in ovarian cancer (OC) are unknown. To identify regulatory elements (RE) and genes perturbed by acquired non-coding variants, here we establish epigenomic and transcriptomic landscapes of primary ... Full text Cite

Super-Enhancer-Associated LncRNA UCA1 Interacts Directly with AMOT to Activate YAP Target Genes in Epithelial Ovarian Cancer.

Journal Article iScience · July 2019 Long noncoding RNAs (lncRNAs) have emerged as critical regulators of tumorigenesis, and yet their mechanistic roles remain challenging to characterize. Here, we integrate functional proteomics with lncRNA-interactome profiling to characterize Urothelial Ca ... Full text Cite

A transcriptome-wide association study of high-grade serous epithelial ovarian cancer identifies new susceptibility genes and splice variants.

Journal Article Nature genetics · May 2019 We sought to identify susceptibility genes for high-grade serous ovarian cancer (HGSOC) by performing a transcriptome-wide association study of gene expression and splice junction usage in HGSOC-relevant tissue types (N = 2,169) and the largest genome-wide ... Full text Cite

RNA editing in nascent RNA affects pre-mRNA splicing.

Journal Article Genome research · June 2018 In eukaryotes, nascent RNA transcripts undergo an intricate series of RNA processing steps to achieve mRNA maturation. RNA editing and alternative splicing are two major RNA processing steps that can introduce significant modifications to the final gene pr ... Full text Cite

Optimizing exosomal RNA isolation for RNA-Seq analyses of archival sera specimens.

Journal Article PloS one · January 2018 Exosomes are endosome-derived membrane vesicles that contain proteins, lipids, and nucleic acids. The exosomal transcriptome mediates intercellular communication, and represents an understudied reservoir of novel biomarkers for human diseases. Next-generat ... Full text Cite

Global analyses of endonucleolytic cleavage in mammals reveal expanded repertoires of cleavage-inducing small RNAs and their targets.

Journal Article Nucleic acids research · April 2016 In mammals, small RNAs are important players in post-transcriptional gene regulation. While their roles in mRNA destabilization and translational repression are well appreciated, their involvement in endonucleolytic cleavage of target RNAs is poorly unders ... Full text Cite

Alternative splicing modulated by genetic variants demonstrates accelerated evolution regulated by highly conserved proteins.

Journal Article Genome research · April 2016 Identification of functional genetic variants and elucidation of their regulatory mechanisms represent significant challenges of the post-genomic era. A poorly understood topic is the involvement of genetic variants in mediating post-transcriptional RNA pr ... Full text Cite

Genomic analysis of ADAR1 binding and its involvement in multiple RNA processing pathways.

Journal Article Nature communications · March 2015 Adenosine deaminases acting on RNA (ADARs) are the primary factors underlying adenosine to inosine (A-to-I) editing in metazoans. Here we report the first global study of ADAR1-RNA interaction in human cells using CLIP-seq. A large number of CLIP sites are ... Full text Cite

Noncoding RNAs in human saliva as potential disease biomarkers.

Journal Article Frontiers in genetics · January 2015 Full text Cite

The landscape of microRNA, Piwi-interacting RNA, and circular RNA in human saliva.

Journal Article Clinical chemistry · January 2015 BackgroundExtracellular RNAs (exRNAs) in human body fluids are emerging as effective biomarkers for detection of diseases. Saliva, as the most accessible and noninvasive body fluid, has been shown to harbor exRNA biomarkers for several human disea ... Full text Cite

Latency-associated nuclear antigen of Kaposi sarcoma-associated herpesvirus promotes angiogenesis through targeting notch signaling effector Hey1.

Journal Article Cancer research · April 2014 Notch signaling has been implicated in the pathogenesis of Kaposi sarcoma. Kaposi sarcoma is an angioproliferative neoplasm that originates from Kaposi sarcoma-associated herpesvirus (KSHV) infection. Previously, we showed that the KSHV LANA protein can st ... Full text Cite

MicroRNAs and unusual small RNAs discovered in Kaposi's sarcoma-associated herpesvirus virions.

Journal Article Journal of virology · December 2012 It is widely held that any given virus uses only one type of nucleic acid for genetic information storage. However, this consensus has been challenged slightly by several recent studies showing that many RNA species are present within a range of DNA viruse ... Full text Cite

Kaposi's sarcoma-associated herpesvirus-encoded microRNA miR-K12-11 attenuates transforming growth factor beta signaling through suppression of SMAD5.

Journal Article Journal of virology · February 2012 Kaposi's sarcoma-associated herpesvirus (KSHV) encodes 12 pre-microRNAs (pre-miRNAs). Current studies have shown that these miRNAs are involved in regulation of viral and host gene expression, implicating a role in the maintenance of viral latency and supp ... Full text Cite

Kaposi's sarcoma-associated herpesvirus-encoded latency-associated nuclear antigen reduces interleukin-8 expression in endothelial cells and impairs neutrophil chemotaxis by degrading nuclear p65.

Journal Article Journal of virology · September 2011 Latency-associated nuclear antigen 1 (LANA-1) of Kaposi's sarcoma-associated herpesvirus (KSHV) is the major viral latent protein and functions as a multifaceted protein. Here, we report that LANA-1 attenuates the endothelial response to tumor necrosis fac ... Full text Cite

A human herpesvirus miRNA attenuates interferon signaling and contributes to maintenance of viral latency by targeting IKKε.

Journal Article Cell research · May 2011 Type I interferon (IFN) signaling is the principal response mediating antiviral innate immunity. IFN transcription is dependent upon the activation of transcription factors IRF3/IRF7 and NF-κB. Many viral proteins have been shown as being capable of interf ... Full text Cite

Looking at Kaposi's Sarcoma-Associated Herpesvirus-Host Interactions from a microRNA Viewpoint.

Journal Article Frontiers in microbiology · January 2011 Kaposi's sarcoma-associated herpesvirus (KSHV), also called human herpesvirus 8, belongs to the gamma herpesviruses and is the etiological agent of Kaposi's sarcoma, primary effusion lymphoma, and some types of multicentric Castleman's disease. In vivo, KS ... Full text Cite

miR-K12-7-5p encoded by Kaposi's sarcoma-associated herpesvirus stabilizes the latent state by targeting viral ORF50/RTA.

Journal Article PloS one · January 2011 Seventeen miRNAs encoded by Kaposi's sarcoma-associated herpesvirus (KSHV) have been identified and their functions have begun to be characterized. Among these miRNAs, we report here that miR-K12-7 directly targets the replication and transcription activat ... Full text Cite

Characterization of a thermostable alkaline phosphatase from a novel species Thermus yunnanensis sp. nov. and investigation of its cobalt activation at high temperature.

Journal Article Biochimica et biophysica acta · June 2005 A thermostable alkaline phosphatase with high specific activity and thermal resistance was purified from a novel species of Thermus sp. named as Thermus yunnanensis sp. nov. The enzyme contains a single peptide with a molecular mass of about 52 kDa on SDS- ... Full text Cite