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Article ; Online: Single-cell epigenome analysis identifies molecular events controlling direct conversion of human fibroblasts to pancreatic ductal-like cells.

Fei, Liangru / Zhang, Kaiyang / Poddar, Nikita / Hautaniemi, Sampsa / Sahu, Biswajyoti

2023 Volume 58, Issue 18, Page(s) 1701–1715.e8

Abstract: Cell fate can be reprogrammed by ectopic expression of lineage-specific transcription factors (TFs). However, the exact cell state transitions during transdifferentiation are still poorly understood. Here, we have generated pancreatic exocrine cells of ... ...

Abstract	Cell fate can be reprogrammed by ectopic expression of lineage-specific transcription factors (TFs). However, the exact cell state transitions during transdifferentiation are still poorly understood. Here, we have generated pancreatic exocrine cells of ductal epithelial identity from human fibroblasts using a set of six TFs. We mapped the molecular determinants of lineage dynamics using a factor-indexing method based on single-nuclei multiome sequencing (FI-snMultiome-seq) that enables dissecting the role of each individual TF and pool of TFs in cell fate conversion. We show that transition from mesenchymal fibroblast identity to epithelial pancreatic exocrine fate involves two deterministic steps: an endodermal progenitor state defined by activation of HHEX with FOXA2 and SOX17 and a temporal GATA4 activation essential for the maintenance of pancreatic cell fate program. Collectively, our data suggest that transdifferentiation-although being considered a direct cell fate conversion method-occurs through transient progenitor states orchestrated by stepwise activation of distinct TFs.
MeSH term(s)	Humans ; Epigenome ; Pancreas ; Fibroblasts ; Cell Differentiation/genetics ; Cell Transdifferentiation/genetics
Language	English
Publishing date	2023-09-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2054967-2
ISSN	1878-1551 ; 1534-5807
ISSN (online)	1878-1551
ISSN	1534-5807
DOI	10.1016/j.devcel.2023.08.023
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Article ; Online: Transposable elements as tissue-specific enhancers in cancers of endodermal lineage.

Karttunen, Konsta / Patel, Divyesh / Xia, Jihan / Fei, Liangru / Palin, Kimmo / Aaltonen, Lauri / Sahu, Biswajyoti

Nature communications

2023 Volume 14, Issue 1, Page(s) 5313

Abstract: Transposable elements (TE) are repetitive genomic elements that harbor binding sites for human transcription factors (TF). A regulatory role for TEs has been suggested in embryonal development and diseases such as cancer but systematic investigation of ... ...

Abstract	Transposable elements (TE) are repetitive genomic elements that harbor binding sites for human transcription factors (TF). A regulatory role for TEs has been suggested in embryonal development and diseases such as cancer but systematic investigation of their functions has been limited by their widespread silencing in the genome. Here, we utilize unbiased massively parallel reporter assay data using a whole human genome library to identify TEs with functional enhancer activity in two human cancer types of endodermal lineage, colorectal and liver cancers. We show that the identified TE enhancers are characterized by genomic features associated with active enhancers, such as epigenetic marks and TF binding. Importantly, we identify distinct TE subfamilies that function as tissue-specific enhancers, namely MER11- and LTR12-elements in colon and liver cancers, respectively. These elements are bound by distinct TFs in each cell type, and they have predicted associations to differentially expressed genes. In conclusion, these data demonstrate how different cancer types can utilize distinct TEs as tissue-specific enhancers, paving the way for comprehensive understanding of the role of TEs as bona fide enhancers in the cancer genomes.
MeSH term(s)	Humans ; DNA Transposable Elements/genetics ; Liver Neoplasms/genetics ; Regulatory Sequences, Nucleic Acid ; Binding Sites ; Biological Assay ; Transcription Factors/genetics
Chemical Substances	DNA Transposable Elements ; Transcription Factors
Language	English
Publishing date	2023-09-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-41081-4
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Article ; Online: Role of MCM2–7 protein phosphorylation in human cancer cells

Liangru Fei / Hongtao Xu

Cell & Bioscience, Vol 8, Iss 1, Pp 1-

2018 Volume 8

Abstract: Abstract A heterohexameric complex composed of minichromosome maintenance protein 2–7 (MCM2–7), which acts as a key replicative enzyme in eukaryotes, is crucial for initiating DNA synthesis only once per cell cycle. The MCM complex remains inactive ... ...

Abstract	Abstract A heterohexameric complex composed of minichromosome maintenance protein 2–7 (MCM2–7), which acts as a key replicative enzyme in eukaryotes, is crucial for initiating DNA synthesis only once per cell cycle. The MCM complex remains inactive through the G1 phase, until the S phase, when it is activated to initiate replication. During the transition from the G1 to S phase, the MCM undergoes multisite phosphorylation, an important change that promotes subsequent assembly of other replisome members. Phosphorylation is crucial for the regulation of MCM activity and function. MCMs can be phosphorylated by multiple kinases and these phosphorylation events are involved not only in DNA replication but also cell cycle progression and checkpoint response. Dysfunctional phosphorylation of MCMs appears to correlate with the occurrence and development of cancers. In this review, we summarize the currently available data regarding the regulatory mechanisms and functional consequences of MCM phosphorylation and seek the probability that protein kinase inhibitor can be used therapeutically to target MCM phosphorylation in cancer.
Keywords	MCM ; Phosphorylation ; DNA replication ; Checkpoint response ; Cell cycle ; Biotechnology ; TP248.13-248.65 ; Biology (General) ; QH301-705.5 ; Biochemistry ; QD415-436
Subject code	612
Language	English
Publishing date	2018-07-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Role of MCM2-7 protein phosphorylation in human cancer cells.

Fei, Liangru / Xu, Hongtao

Cell & bioscience

2018 Volume 8, Page(s) 43

Abstract: A heterohexameric complex composed of minichromosome maintenance protein 2-7 (MCM2-7), which acts as a key replicative enzyme in eukaryotes, is crucial for initiating DNA synthesis only once per cell cycle. The MCM complex remains inactive through the G1 ...

Abstract	A heterohexameric complex composed of minichromosome maintenance protein 2-7 (MCM2-7), which acts as a key replicative enzyme in eukaryotes, is crucial for initiating DNA synthesis only once per cell cycle. The MCM complex remains inactive through the G1 phase, until the S phase, when it is activated to initiate replication. During the transition from the G1 to S phase, the MCM undergoes multisite phosphorylation, an important change that promotes subsequent assembly of other replisome members. Phosphorylation is crucial for the regulation of MCM activity and function. MCMs can be phosphorylated by multiple kinases and these phosphorylation events are involved not only in DNA replication but also cell cycle progression and checkpoint response. Dysfunctional phosphorylation of MCMs appears to correlate with the occurrence and development of cancers. In this review, we summarize the currently available data regarding the regulatory mechanisms and functional consequences of MCM phosphorylation and seek the probability that protein kinase inhibitor can be used therapeutically to target MCM phosphorylation in cancer.
Language	English
Publishing date	2018-07-24
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2593367-X
ISSN	2045-3701
ISSN	2045-3701
DOI	10.1186/s13578-018-0242-2
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Economic Burden and Influencing Factors of Acute Gastroenteritis in China

Yue Huo / Fei Gao / Jiayu Wang / Zhongwei Liu / Liangru Zhou / Baiyang Gu / Xin Zhang / Yi Ma

Frontiers in Public Health, Vol

A Population-Based Face to Face Survey in 2018

2022 Volume 10

Abstract: BackgroundAcute gastroenteritis is an important and highly prevalent public health problem worldwide. The purpose of this study was to assess the economic burden of disease and its influencing factors in patients with acute gastroenteritis in ... ...

Abstract	BackgroundAcute gastroenteritis is an important and highly prevalent public health problem worldwide. The purpose of this study was to assess the economic burden of disease and its influencing factors in patients with acute gastroenteritis in Heilongjiang Province, China.MethodsA multi-stage stratified random sampling method was used in a face-to-face household survey in 2018. Demographic and socioeconomic characteristics, clinical symptoms, suspicious dietary history, and disease treatment information were collected from 19,647 respondents. One-way analysis of variance and multiple stepwise regression analysis were used to investigate the factors associated with the economic burden of acute gastroenteritis. Quantitative risk analysis and sensitivity analysis were performed to estimate the uncertainty and risk factors of the economic burden of acute gastroenteritis.ResultsThe total economic burden of patients with acute gastroenteritis was 63,969.22 CNY (Chinese Yuan), of which the direct economic burden accounted for 63.82%; the per capita economic burden was 131.35 CNY per month. Age, region, disease duration, and disease treatment were the main factors significantly associated with the economic burden of acute gastroenteritis (P < 0.05). The average economic burden of patients with acute gastroenteritis was approximately 571.84 CNY/person (95% CI: 227–1,459). Sensitivity analysis showed that the greatest impact was from the indirect economic burden.ConclusionsAcute gastroenteritis brings a substantial health burden to patients due to its high incidence. The economic burden of self-purchased drugs and the indirect economic burden of patients cannot be ignored. To better estimate the economic burden of acute gastroenteritis in China, further studies on the pathogen-specific economic burden of acute gastroenteritis are required.
Keywords	acute gastroenteritis ; economic burden ; influential factors ; self-reported suspected etiology ; population surveillance ; Public aspects of medicine ; RA1-1270
Subject code	610
Language	English
Publishing date	2022-06-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Economic Burden and Influencing Factors of Acute Gastroenteritis in China: A Population-Based Face to Face Survey in 2018.

Huo, Yue / Gao, Fei / Wang, Jiayu / Liu, Zhongwei / Zhou, Liangru / Gu, Baiyang / Zhang, Xin / Ma, Yi

Frontiers in public health

2022 Volume 10, Page(s) 905458

Abstract: Background: Acute gastroenteritis is an important and highly prevalent public health problem worldwide. The purpose of this study was to assess the economic burden of disease and its influencing factors in patients with acute gastroenteritis in ... ...

Abstract	Background: Acute gastroenteritis is an important and highly prevalent public health problem worldwide. The purpose of this study was to assess the economic burden of disease and its influencing factors in patients with acute gastroenteritis in Heilongjiang Province, China. Methods: A multi-stage stratified random sampling method was used in a face-to-face household survey in 2018. Demographic and socioeconomic characteristics, clinical symptoms, suspicious dietary history, and disease treatment information were collected from 19,647 respondents. One-way analysis of variance and multiple stepwise regression analysis were used to investigate the factors associated with the economic burden of acute gastroenteritis. Quantitative risk analysis and sensitivity analysis were performed to estimate the uncertainty and risk factors of the economic burden of acute gastroenteritis. Results: The total economic burden of patients with acute gastroenteritis was 63,969.22 CNY (Chinese Yuan), of which the direct economic burden accounted for 63.82%; the per capita economic burden was 131.35 CNY per month. Age, region, disease duration, and disease treatment were the main factors significantly associated with the economic burden of acute gastroenteritis ( Conclusions: Acute gastroenteritis brings a substantial health burden to patients due to its high incidence. The economic burden of self-purchased drugs and the indirect economic burden of patients cannot be ignored. To better estimate the economic burden of acute gastroenteritis in China, further studies on the pathogen-specific economic burden of acute gastroenteritis are required.
MeSH term(s)	China/epidemiology ; Cost of Illness ; Financial Stress ; Gastroenteritis/epidemiology ; Humans ; Incidence
Language	English
Publishing date	2022-06-03
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2711781-9
ISSN	2296-2565 ; 2296-2565
ISSN (online)	2296-2565
ISSN	2296-2565
DOI	10.3389/fpubh.2022.905458
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Article ; Online: Comprehensive characterization of the embryonic factor LEUTX.

iScience

2023 Volume 26, Issue 3, Page(s) 106172

Abstract: The paired-like homeobox transcription factor LEUTX is expressed in human preimplantation embryos between the 4- and 8-cell stages, and then silenced in somatic tissues. To characterize the function of LEUTX, we performed a multiomic characterization of ... ...

Abstract	The paired-like homeobox transcription factor LEUTX is expressed in human preimplantation embryos between the 4- and 8-cell stages, and then silenced in somatic tissues. To characterize the function of LEUTX, we performed a multiomic characterization of LEUTX using two proteomics methods and three genome-wide sequencing approaches. Our results show that LEUTX stably interacts with the EP300 and CBP histone acetyltransferases through its 9 amino acid transactivation domain (9aaTAD), as mutation of this domain abolishes the interactions. LEUTX targets genomic cis-regulatory sequences that overlap with repetitive elements, and through these elements it is suggested to regulate the expression of its downstream genes. We find LEUTX to be a transcriptional activator, upregulating several genes linked to preimplantation development as well as 8-cell-like markers, such as DPPA3 and ZNF280A. Our results support a role for LEUTX in preimplantation development as an enhancer binding protein and as a potent transcriptional activator.
Language	English
Publishing date	2023-02-09
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2023.106172
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Article ; Online: RACK1 promotes lung cancer cell growth via an MCM7/RACK1/ Akt signaling complex.

Fei, Liangru / Ma, Yinan / Zhang, Meiyu / Liu, Xiaofang / Luo, Yuan / Wang, Congcong / Zhang, Haiyan / Zhang, Wenzhu / Han, Yuchen

Oncotarget

2017 Volume 8, Issue 25, Page(s) 40501–40513

Abstract: MCM7, a member of the miniature chromosome maintenance (MCM) protein family, is crucial for the initiation of DNA replication and proliferation in eukaryotic cells. In this report, we demonstrate that RACK1 regulates cell growth and cell cycle ... ...

Abstract	MCM7, a member of the miniature chromosome maintenance (MCM) protein family, is crucial for the initiation of DNA replication and proliferation in eukaryotic cells. In this report, we demonstrate that RACK1 regulates cell growth and cell cycle progression in human non-small-cell lung cancer by mediating MCM7 phosphorylation through an MCM7/RACK1/Akt signaling complex. RACK1 functions as a central scaffold that brings Akt into physical proximity with MCM7. Overexpression of RACK1 increases interactions between Akt and MCM7 and promotes Akt-dependent MCM7 phosphorylation, which in turn increases MCM7 binding to chromatin and MCM complex formation. Together, these changes promote DNA replication and cell proliferation. Our findings reveal a novel signaling pathway that regulates growth in non-small cell lung cancer.
Language	English
Publishing date	2017-06-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.17120
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Article ; Online: Lamin B2 binding to minichromosome maintenance complex component 7 promotes non-small cell lung carcinogenesis.

Ma, Yinan / Fei, Liangru / Zhang, Meiyu / Zhang, Wenzhu / Liu, Xiaofang / Wang, Congcong / Luo, Yuan / Zhang, Haiyan / Han, Yuchen

Oncotarget

2017 Volume 8, Issue 62, Page(s) 104813–104830

Abstract: We investigated the role of lamin B2 in non-small cell lung cancer (NSCLC). We detected higher lamin B2 expression in 20 NSCLC tumor tissues obtained from The Cancer Genome Atlas than in adjacent normal lung tissues. LMNB2-RNAi knockdown in A549 and ... ...

Abstract	We investigated the role of lamin B2 in non-small cell lung cancer (NSCLC). We detected higher lamin B2 expression in 20 NSCLC tumor tissues obtained from The Cancer Genome Atlas than in adjacent normal lung tissues. LMNB2-RNAi knockdown in A549 and H1299 NSCLC cells inhibited colony formation, cell proliferation and G1-S cell cycle progression while increasing apoptosis. LMNB2 overexpression had the opposite effects. Tumor xenograft experiments showed diminished tumor growth with LMNB2 knockdown H1299 cells than with controls. Yeast two-hybrid studies revealed minichromosome maintenance complex component 7 (MCM7) to be a binding partner of lamin B2, which was confirmed by co-immunoprecipitation and co-localization studies. Lamin B2 binding enhanced DNA binding and helicase activities of MCM7. Deletion analysis with MCM7-N, MCM7-M or MCM7-C mutant proteins showed that lamin B2 binds to the C-terminus of MCM7, and competes with the binding of the tumor suppressor retinoblastoma (RB) protein. Immunohistochemical analysis of 150 NSCLC patient samples revealed that both lamin B2 and MCM7 levels positively correlated with histological grade and tumor TNM stage. Moreover, high lamin B2 and MCM7 levels correlated with shorter overall survival of NSCLC patients. In sum, these results show that lamin B2 interaction with MCM7 promotes NSCLC progression.
Language	English
Publishing date	2017-12-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.20338
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Article ; Online: Camrelizumab and apatinib plus induction chemotherapy and concurrent chemoradiotherapy in stage N3 nasopharyngeal carcinoma: a phase 2 clinical trial.

Liang, Hu / Jiang, Yao-Fei / Liu, Guo-Ying / Wang, Lin / Wang, Jian-Wei / Lu, Nian / Xia, Wei-Xiong / Ke, Liang-Ru / Ye, Yan-Fang / Duan, Jin-Lin / Bei, Wei-Xin / Dong, Shu-Hui / Li, Wang-Zhong / Liu, Li-Ting / Zhao, Chong / Xie, Changqing / Xiang, Yan-Qun

Nature communications

2024 Volume 15, Issue 1, Page(s) 1029

Abstract: The antiangiogenic agent apatinib has been shown to clinically improve responses to immune checkpoint inhibitors in several cancer types. Patients with N3 nasopharyngeal carcinoma have a high risk of distant metastasis, however, if the addition of ... ...

Abstract	The antiangiogenic agent apatinib has been shown to clinically improve responses to immune checkpoint inhibitors in several cancer types. Patients with N3 nasopharyngeal carcinoma have a high risk of distant metastasis, however, if the addition of immunotherapy to standard treatment could improve efficacy is unclear. In this phase II clinical trial (ChiCTR2000032317), 49 patients with stage T
MeSH term(s)	Humans ; Nasopharyngeal Carcinoma/drug therapy ; Nasopharyngeal Carcinoma/pathology ; Induction Chemotherapy/adverse effects ; Nasopharyngeal Neoplasms/drug therapy ; Nasopharyngeal Neoplasms/pathology ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Cisplatin/therapeutic use ; Chemoradiotherapy/adverse effects ; Pyridines ; Antibodies, Monoclonal, Humanized
Chemical Substances	camrelizumab (73096E137E) ; apatinib (5S371K6132) ; Cisplatin (Q20Q21Q62J) ; Pyridines ; Antibodies, Monoclonal, Humanized
Language	English
Publishing date	2024-02-03
Publishing country	England
Document type	Clinical Trial, Phase II ; Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-45126-0
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