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Kyeoung-Hwa Kim, You-Mi Seo, Eun-Young Kim, Su-Yeon Lee, Jini Kwon, Jung-Jae Ko, Kyung-Ah Lee
Previously, we reported that Sebox is a new maternal effect gene (MEG) that is required for early embryo development beyond the two-cell (2C) stage because this gene orchestrates the expression of important genes for zygotic genome activation (ZGA). However, regulators of Sebox expression remain unknown. Therefore, the objectives of the present study were to use bioinformatics tools to identify such regulatory microRNAs (miRNAs) and to determine the effects of the identified miRNAs on Sebox expression. Using computational algorithms, we identified a motif within the 3'UTR of Sebox mRNA that is specific to the seed region of the miR-125 family, which includes miR-125a-5p, miR-125b-5p and miR-351-5p...
November 2016: Open Biology
Jakub Stanislaw Nowak, Fruzsina Hobor, Angela Downie Ruiz Velasco, Nila Roy Choudhury, Gregory Heikel, Alastair Kerr, Andres Ramos, Gracjan Michlewski
Lin28a inhibits the biogenesis of let-7 miRNAs by triggering the polyuridylation and degradation of their precursors by terminal uridylyltransferases TUT4/7 and 3'-5' exoribonuclease Dis3l2, respectively. Previously, we showed that Lin28a also controls the production of neuro-specific miRNA-9 via a polyuridylation-independent mechanism. Here we reveal that the sequences and structural characteristics of pre-let-7 and pre-miRNA-9 are eliciting two distinct modes of binding to Lin28a. We present evidence that Dis3l2 controls miRNA-9 production...
November 23, 2016: RNA
Lila E Mullany, Jennifer S Herrick, Roger K Wolff, Martha L Slattery
We have shown that single nucleotide polymorphisms (SNPs) in microRNA (miRNA) genes, miRNA target genes, and miRNA biogenesis genes minimally contribute to colon cancer risk. It is possible that these SNPs alter survival. We analyzed 565 SNPs in or adjacent to microRNAs, target genes, or biogenesis genes, using 1115 cases and 1173 controls; 837 cases had survival information. We tested SNPs for associations with colorectal cancer (CRC) survival using a Cox proportional hazard model adjusting for age, study center, gender, AJCC disease stage, and MSI tumor status...
November 18, 2016: Genes, Chromosomes & Cancer
Tianzhen Wang, Yan He, Yuanyuan Zhu, Mingwei Chen, Mingjiao Weng, Chao Yang, Yan Zhang, Ning Ning, Ran Zhao, Weiwei Yang, Yinji Jin, Jing Li, Riju James Rajkumar Ezakiel Redpath, Lei Zhang, Xiaoming Jin, Zhaohua Zhong, Fengmin Zhang, Yunwei Wei, Guomin Shen, Dong Wang, Ying Liu, Guangyu Wang, Xiaobo Li
Lin28A and Lin28B are highly conserved RNA binding proteins with similar structure and functions. Recent studies demonstrated that both of them act as oncogenes and promote cancer progression. However, few researches compared the expression and functions of both oncogenes in human malignant tumors at same time. Additionally, although the expression and role of Lin28B in colon cancer is frequently reported, the expression and functions of Lin28A in colon cancer are largely unknown. In this study, we have systematically evaluated the expressional pattern, mutation status and correlation of both Lin28A and Lin28B in colon cancer tissues for the first time, and compared the roles of Lin28A and Lin28B in the proliferation, migration, invasion and apoptosis of colon cancer cells in vitro...
October 25, 2016: Oncotarget
Tian Fang, Hongwei Lv, Fuquan Wu, Changzheng Wang, Ting Li, Guishuai Lv, Liang Tang, Linna Guo, Shanhua Tang, Dan Cao, Mengchao Wu, Wen Yang, Hongyang Wang
Accumulating evidence suggests that cancer stem cells (CSCs), a small subset of cancer cells, are responsible for tumor initiation, progression, relapse and metastasis. Musashi 2 (MSI2), a RNA-binding protein, was proposed to be a potent oncogene playing key roles in myeloid leukemia and gastrointestinal malignancies. However, it remains elusive how MSI2 regulates stem cell features in HCC. Herein, we demonstrated that MSI2 was highly expressed in liver CSCs. Overexpression or knockdown of MSI2 altered CSC-related gene expression, self-renewal as well as resistance to chemotherapy in HCC cell lines...
January 1, 2017: Cancer Letters
Yuanyuan Hao, Qun Lu, Guodong Yang, Aiqun Ma
BACKGROUND: Myocardial remodeling and cardiac dysfunction prevention may represent a therapeutic approach to reduce mortality in patients with myocardial infarction (MI). We investigated the effects of Lin28a in experimental MI models, as well as the mechanisms underlying these effects. METHODS: Left anterior descending (LAD) coronary artery ligation was used to construct an MI-induced injury model. Neonatal cardiomyocytes were isolated and cultured to investigate the mechanisms underlying the protective effects of Lin28a against MI-induced injury...
October 28, 2016: Biochemical and Biophysical Research Communications
Xiao Qi Wang, Chung Mau Lo, Lin Chen, Elly S-W Ngan, Aimin Xu, Randy Yc Poon
The mechanisms of how signaling pathways are coordinated and integrated for the maintenance of the self-renewal of human embryonic stem cells (hESCs) and the acquisition of pluripotency in reprogramming are still only partly understood. CDK1 is a key regulator of mitosis. Recently, CDK1 has been shown to be involved in regulating self-renewal of stem cells, even though the mechanistic role of how CDK1 regulates pluripotency is unknown. In this report, we aim to understand how CDK1 can control pluripotency by reducing CDK1 activity to a level that has no effect on cell cycle progression...
September 16, 2016: Cell Death and Differentiation
Daniel T Peters, Herman K H Fung, Vladimir M Levdikov, Tobias Irmscher, Fiona C Warrander, Sandra J Greive, Oleg Kovalevskiy, Harry V Isaacs, Mark Coles, Alfred A Antson
Lin28A is a post-transcriptional regulator of gene expression that interacts with and negatively regulates the biogenesis of let-7 family miRNAs. Recent data suggested that Lin28A also binds the putative tumor suppressor miR-363, a member of the 106~363 cluster of miRNAs. Affinity for this miRNA and the stoichiometry of the protein-RNA complex are unknown. Characterization of human Lin28's interaction with RNA has been complicated by difficulties in producing stable RNA-free protein. We have engineered a maltose binding protein fusion with Lin28, which binds let-7 miRNA with a Kd of 54...
September 13, 2016: Biochemistry
Yong-Hee Rhee, Tae-Ho Kim, A-Young Jo, Mi-Yoon Chang, Chang-Hwan Park, Sang-Mi Kim, Jae-Jin Song, Sang-Min Oh, Sang-Hoon Yi, Hyeon Ho Kim, Bo-Hyun You, Jin-Wu Nam, Sang-Hun Lee
The original properties of tissue-specific stem cells, regardless of their tissue origins, are inevitably altered during in vitro culturing, lessening the clinical and research utility of stem cell cultures. Specifically, neural stem cells derived from the ventral midbrain lose their dopamine neurogenic potential, ventral midbrain-specific phenotypes, and repair capacity during in vitro cell expansion, all of which are critical concerns in using the cultured neural stem cells in therapeutic approaches for Parkinson's disease...
August 18, 2016: Brain: a Journal of Neurology
Gregory Heikel, Nila Roy Choudhury, Gracjan Michlewski
Trim25 is a member of the tripartite motif family of E3 ubiquitin ligases. It plays major roles in innate immunity and defence against viral infection, control of cell proliferation and migration of cancer cells. Recent work identified Trim25 as being able to bind to RNA and to regulate Lin28a-mediated uridylation of pre-let-7. Here we review the current knowledge of the role of Trim25 in development, disease and RNA metabolism.
August 15, 2016: Biochemical Society Transactions
Honghong Shen, Lin Zhao, Xiaolong Feng, Cong Xu, Congying Li, Yun Niu
Having previously demonstrated the co-expression status of the Lin28A and androgen receptor (AR) in ER-/Her2+ breast cancer, we tested the hypothesis that Lin28A can activate AR and promotes growth of ER-/Her2+ breast cancer. The expression of Lin28A and AR were examined after Lin28A siRNA and Lin28A plasmid were transfected into ER-/Her2+ breast cancer cells. Chromatin immune-precipitation (ChIP) analysis and Luciferase Assays were used to evaluate the effect of Lin28A and c-myc on AR promoter activity. MTT assays, Boyden chamber invasion assays, colony formation assays and flow cytometry analysis were performed...
August 2, 2016: Oncotarget
A Pirnia, K Parivar, M Hemadi, P Yaghmaei, M Gholami
This study investigated the effect of spermatogonial stem cell encapsulated in alginate hydrogel during cryopreservation, as cells were protected against damage during cryopreservation within the hydrogel. Spermatogonial stem cells were isolated from the testes of Balb/c mice pups (6 days old), purified in laminin-coated dishes and CD90.1 microbeads, encapsulated in alginate hydrogel and then cryopreserved. After thawing, cell viability and Spermatogonial stem cell (SSC) colony diameter were evaluated. After RNA was isolated and cDNA was synthesised, the expression of stemness genes was considered using RT real-time PCR...
July 29, 2016: Andrologia
Jin Zhang, Sutheera Ratanasirintrawoot, Sriram Chandrasekaran, Zhaoting Wu, Scott B Ficarro, Chunxiao Yu, Christian A Ross, Davide Cacchiarelli, Qing Xia, Marc Seligson, Gen Shinoda, Wen Xie, Patrick Cahan, Longfei Wang, Shyh-Chang Ng, Supisara Tintara, Cole Trapnell, Tamer Onder, Yuin-Han Loh, Tarjei Mikkelsen, Piotr Sliz, Michael A Teitell, John M Asara, Jarrod A Marto, Hu Li, James J Collins, George Q Daley
The RNA-binding proteins LIN28A and LIN28B play critical roles in embryonic development, tumorigenesis, and pluripotency, but their exact functions are poorly understood. Here, we show that, like LIN28A, LIN28B can function effectively with NANOG, OCT4, and SOX2 in reprogramming to pluripotency and that reactivation of both endogenous LIN28A and LIN28B loci are required for maximal reprogramming efficiency. In human fibroblasts, LIN28B is activated early during reprogramming, while LIN28A is activated later during the transition to bona fide induced pluripotent stem cells (iPSCs)...
July 7, 2016: Cell Stem Cell
Craig K Docherty, Ian P Salt, John R Mercer
BACKGROUND: Loss of a cell's capacity to generate sufficient energy for cellular functions is a key hallmark of the ageing process and ultimately leads to a variety of important age-related pathologies such as cancer, Parkinson's disease and atherosclerosis. Regenerative medicine has sought to reverse these pathologies by reprogramming somatic cells to a more juvenile energetic state using a variety of stem cell factors. One of these factors, Lin28, is considered a candidate for modification in the reprogramming of cellular energetics to ameliorate the ageing process while retaining cell phenotype...
2016: Stem Cell Research & Therapy
Domenico Albino, Gianluca Civenni, Cecilia Dallavalle, Martina Roos, Hartmut Jahns, Laura Curti, Simona Rossi, Sandra Pinton, Gioacchino D'Ambrosio, Fausto Sessa, Jonathan Hall, Carlo V Catapano, Giuseppina M Carbone
Although cancer stem-like cells (CSC) are thought to be the most tumorigenic, metastatic, and therapy-resistant cell subpopulation within human tumors, current therapies target bulk tumor cells while tending to spare CSC. In seeking to understand mechanisms needed to acquire and maintain a CSC phenotype in prostate cancer, we investigated connections between the ETS transcription factor ESE3/EHF, the Lin28/let-7 microRNA axis, and the CSC subpopulation in this malignancy. In normal cells, we found that ESE3/EHF bound and repressed promoters for the Lin28A and Lin28B genes while activating transcription and maturation of the let-7 microRNAs...
June 15, 2016: Cancer Research
Nils Degrauwe, Tommy B Schlumpf, Michalina Janiszewska, Patricia Martin, Alexandra Cauderay, Paolo Provero, Nicolo Riggi, Mario-L Suvà, Renato Paro, Ivan Stamenkovic
Cancer stem cells (CSCs) can drive tumor growth, and their maintenance may rely on post-transcriptional regulation of gene expression, including that mediated by microRNAs (miRNAs). The let-7 miRNA family has been shown to induce differentiation by silencing stem cell programs. Let-7-mediated target gene suppression is prevented by LIN28A/B, which reduce let-7 biogenesis in normal embryonic and some cancer stem cells and ensure maintenance of stemness. Here, we find that glioblastoma stem cells (GSCs) lack LIN28 and express both let-7 and their target genes, suggesting LIN28-independent protection from let-7 silencing...
May 24, 2016: Cell Reports
Dao-Rong Hou, Yong Jin, Xiao-Wei Nie, Man-Ling Zhang, Na Ta, Li-Hua Zhao, Ning Yang, Yuan Chen, Zhao-Qiang Wu, Hai-Bin Jiang, Yan-Ru Li, Qing-Yuan Sun, Yi-Fan Dai, Rong-Feng Li
Efficient isolation of embryonic stem (ES) cells from pre-implantation porcine embryos has remained a challenge. Here, we describe the derivation of porcine embryonic stem-like cells (pESLCs) by seeding the isolated inner cell mass (ICM) from in vitro-produced porcine blastocyst into α-MEM with basic fibroblast growth factor (bFGF). The pESL cells kept the normal karyotype and displayed flatten clones, similar in phenotype to human embryonic stem cells (hES cells) and rodent epiblast stem cells. These cells exhibited alkaline phosphatase (AP) activity and expressed pluripotency markers such as OCT4, NANOG, SOX2, SSEA-4, TRA-1-60, and TRA-1-81 as determined by both immunofluorescence and RT-PCR...
2016: Scientific Reports
Jose V Medrano, Ana M Martínez-Arroyo, Jose M Míguez, Inmaculada Moreno, Sebastián Martínez, Alicia Quiñonero, Patricia Díaz-Gimeno, Ana I Marqués-Marí, Antonio Pellicer, Jose Remohí, Carlos Simón
The in vitro derivation of human germ cells has attracted interest in the last years, but their direct conversion from human somatic cells has not yet been reported. Here we tested the ability of human male somatic cells to directly convert into a meiotic germ cell-like phenotype by inducing them with a combination of selected key germ cell developmental factors. We started with a pool of 12 candidates that were reduced to 6, demonstrating that ectopic expression of the germ line-related genes PRDM1, PRDM14, LIN28A, DAZL, VASA and SYCP3 induced direct conversion of somatic cells (hFSK (46, XY), and hMSC (46, XY)) into a germ cell-like phenotype in vitro...
2016: Scientific Reports
Seung Ah Choi, Seung-Ki Kim, Ji Yeoun Lee, Kyu-Chang Wang, Chanhee Lee, Ji Hoon Phi
BACKGROUND: Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant brain tumor that almost exclusively develops in young children. AT/RT belongs to the embryonal brain tumor group, comprising primitive tumors recapitulating the early development of the central nervous system during embryogenesis. The loss of SMARCB1 protein expression is a hallmark of AT/RT pathogenesis. LIN28A/B is a key gene in embryonic development and for the maintenance of pluripotency in stem cells. LIN28B might be an important co-player in AT/RT pathogenesis, considering the primitive nature and young age onset of AT/RT...
2016: Cancer Cell International
Annika K Wefers, Sven Lindner, Johannes H Schulte, Ulrich Schüller
LIN28B is a homologue of the RNA-binding protein LIN28A and regulates gene expression during development and carcinogenesis. It is strongly upregulated in a variety of brain tumors, such as medulloblastoma, embryonal tumor with multilayered rosettes (ETMR), atypical teratoid/rhabdoid tumor (AT/RT), or glioblastoma, but the effect of an in vivo overexpression of LIN28B on the developing central nervous system is unknown. We generated transgenic mice that either overexpressed Lin28b in Math1-positive cerebellar granule neuron precursors or in a broad range of Nestin-positive neural precursors...
April 2, 2016: Cerebellum
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