1.LIM domain only 1: an oncogenic transcription cofactor contributing to the tumorigenesis of multiple cancer types.
Guo-Fa ZHAO ; Li-Qin DU ; Lei ZHANG ; You-Chao JIA
Chinese Medical Journal 2021;134(9):1017-1030
The LIM domain only 1 (LMO1) gene belongs to the LMO family of genes that encodes a group of transcriptional cofactors. This group of transcriptional cofactors regulates gene transcription by acting as a key "connector" or "scaffold" in transcription complexes. All LMOs, including LMO1, are important players in the process of tumorigenesis. Unique biological features of LMO1 distinct from other LMO members, such as its tissue-specific expression patterns, interacting proteins, and transcriptional targets, have been increasingly recognized. Studies indicated that LMO1 plays a critical oncogenic role in various types of cancers, including T-cell acute lymphoblastic leukemia, neuroblastoma, gastric cancer, lung cancer, and prostate cancer. The molecular mechanisms underlying such functions of LMO1 have also been investigated, but they are currently far from being fully elucidated. Here, we focus on reviewing the current findings on the role of LMO1 in tumorigenesis, the mechanisms of its oncogenic action, and the mechanisms that drive its aberrant activation in cancers. We also briefly review its roles in the development process and non-cancer diseases. Finally, we discuss the remaining questions and future investigations required for promoting the translation of laboratory findings to clinical applications, including cancer diagnosis and treatment.
Carcinogenesis/genetics*
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DNA-Binding Proteins/genetics*
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Gene Expression Regulation, Neoplastic
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Humans
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LIM Domain Proteins/genetics*
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Male
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Transcription Factors/metabolism*
3.Expressions of bcl-6, lpp and miR-28 genes in diffuse large B cell lymphoma cell lines.
Wei XU ; Jian-Yong LI ; Lei FAN ; Chun QIAO ; Hui YU ; Qiu-Dan SHEN
Journal of Experimental Hematology 2009;17(1):83-87
This study was purposed to explore the expressions of bcl-6, lpp and miR-28 genes in diffuse large B cell lymphoma (DLBCL) cell lines at the levels of gene and protein, and the relationship between them. Northern blot was used to detect bcl-6 and lpp mRNA expression in 8 DLBCL cell lines. Solution hybridization was used to measure miR-28 expression, and Western blot was performed for BCL-6 and LPP protein determinations. The results showed that the expression of bcl-6 mRNA was higher in the cell lines with Ig/BCL-6 translocation (Oc1-ly8, MD903, CTB-1, and MD901), and negative in those without Ig/BCL-6 translocation (HRC57 and K231). The expression of lpp mRNA in CTB-1 cell line was negative. MiR-28 was positive in all cell lines, and the expression levels from high to low were in line as follows: K231, CTB-1, MD903, HRC57, MD901, RCK8, OC1-LY8 and BEVA. BCL-6 protein was also positive in all of cell lines, and the expression levels from high to low were as follows: RCK8, BEVA, MD901, CTB-1, MD903, OC1-LY8, HRC57 and K231. LPP protein was negative in K231 cells, and the expression levels in other cells from high to low were line up as follows: HRC57, OC1-LY8, BEVA, RCK8, CTB-1, MD901 and MD903. The expression levels of bcl-6 and lpp mRNA were not consistent with expression levels of protein. It is concluded that the gene expression levels of bcl-6, lpp and miR-28 are different in various DLBCL cell lines. The expression levels of bcl-6 and lpp mRNA are not parallel with expression levels of protein. The roles of bcl-6, lpp and miR-28 in initiation and development of DLBCL need further investigation.
Cell Line, Tumor
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Cytoskeletal Proteins
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genetics
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DNA-Binding Proteins
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genetics
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Gene Expression
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Humans
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LIM Domain Proteins
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Lymphoma, Large B-Cell, Diffuse
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genetics
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MicroRNAs
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genetics
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Proto-Oncogene Proteins c-bcl-6
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genetics
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RNA, Messenger
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genetics
4.Identification of interaction partners and function analysis of new splicing product of human LMO2 gene.
Wei YUAN ; Shuang YANG ; Wei SUN ; Jun DU ; Chun-Li ZHAI ; Zhao-Qi WANG ; Tian-Hui ZHU
Chinese Journal of Hematology 2008;29(5):325-328
OBJECTIVETo identify the interaction partners of a new splicing product of LMO2 gene (LMO2-C), and study its function in K562 cells.
METHODSMaltose binding protein (MBP) pull down and mammalian two-hybrid assay (MTHA) were used to identify the interaction partners of LMO2-C in K562 cells. Semiquantitative RT-PCR was used to detect the expression of hematopoietic specific gene glycoprotein (GPA) in K562 cells.
RESULTSMBP-LMO2-C fusion protein was expressed and purified in soluble form successfully. Endogenous GATA1 and LDB1 proteins were confirmed to bind to LMO2-C by MBP pull down analysis. The MTHA also showed that LMO2-C had comparable binding affinities to LDB1 with LMO2-L, and over expression of LMO2-C prevented LMO2-L from binding to LDB1, the inhibition rate being (81.13 +/- 0.68)%. RT-PCR results showed that the expression level of GPA was reduced [(51.00 +/- 1.58)%] in K562 cells while LMO2-C overexpressed.
CONCLUSIONLMO2-C can bind endogenous GATA1 and LDB1 protein in K562 cells and down regulates the expression of GPA.
Adaptor Proteins, Signal Transducing ; DNA-Binding Proteins ; genetics ; metabolism ; GATA1 Transcription Factor ; metabolism ; Humans ; K562 Cells ; LIM Domain Proteins ; Maltose-Binding Proteins ; Metalloproteins ; genetics ; metabolism ; Periplasmic Binding Proteins ; Proto-Oncogene Proteins ; RNA Splicing ; Transcription Factors ; metabolism ; Two-Hybrid System Techniques
5.Regulation of E-cadherin promoter activity by LMO2 impact on the progression and metastasis of prostate cancer.
Chinese Journal of Applied Physiology 2013;29(5):385-389
OBJECTIVETo study the abnormal expression of the proto-oncogene LMO2 affect the progression and metastasis mechanism of prostate cancer.
METHODSA series of reporter gene expression vectors carrying different lengths and point mutations of E-cadherin promoter were constructed. These plasmids were separately co-transfected with LMO2 into Lncap cells and the luciferase activity was detected after 24 h.
RESULTSThe overexpression of LMO2 could significantly inhibit the activity of luciferase reporter gene of E-cadherin promoter about 50%. Truncated and point mutation study showed that this was mainly through E-box sites in the promoter region -204/-198.
CONCLUSIONThe proto-oncogene LMO2 can affect the progression and metastasis mechanism of prostate cancer by transcriptional inhibition of E-cadherin.
Adaptor Proteins, Signal Transducing ; genetics ; metabolism ; Cadherins ; genetics ; Cell Line, Tumor ; Genetic Vectors ; Humans ; LIM Domain Proteins ; genetics ; metabolism ; Male ; Neoplasm Metastasis ; Point Mutation ; Promoter Regions, Genetic ; Prostatic Neoplasms ; genetics ; metabolism ; pathology ; Proto-Oncogene Proteins ; genetics ; metabolism
6.Ultrasound-mediated microbubble destruction enhances LMP-1 gene transfection into dendritic cells in vivo.
Rui-feng XU ; Min SHI ; Chang-xuan YOU ; Cheng-wei LÜ ; Rong-cheng LUO ; Wang-jun LIAO
Journal of Southern Medical University 2010;30(10):2327-2332
OBJECTIVETo investigate the transfection efficiency and the optimal conditions of delivering latent membrane protein-1 (LMP-1) gene to dendritic cells (DCs) by ultrasound exposure combined with contrast agent.
METHODSHuman DCs were cultured in vivo and transfected with the recombinant plasmid pEGFP-C3-LMP1 under varying conditions including ultrasound intensities, exposure time and microbubble contrast agent concentration. The transfection efficiency was assessed by fluorescent microscopy and flow cytometry, and the cell viability by trypan blue exclusion test.
RESULTSAn exposure time of 60 s at MI 1.0 with a microbubble contrast agent concentration of 20% resulted in the optimal effect of delivering the recombinant plasmid pEGFP-C3-LMP1 into the DCs, with a transfection efficiency of (14.37∓2.12)%. Over 90% of the transfected cells were viable after the transfection.
CONCLUSIONMicrobubble contrast agent combined with ultrasound exposure can enhance the delivery of recombinant plasmid pEGFP-C3-LMP1 into the DCs.
Adaptor Proteins, Signal Transducing ; genetics ; Cells, Cultured ; Contrast Media ; administration & dosage ; pharmacology ; Cytoskeletal Proteins ; genetics ; Dendritic Cells ; drug effects ; metabolism ; Humans ; LIM Domain Proteins ; genetics ; Microbubbles ; Plasmids ; Transfection ; Ultrasonics
7.Effect of Pinch-3 gene interference of glomerular podocytes on cell morphology and cell traction force.
Yu YANG ; Qingyuan NIU ; Zhenling JI ; Jingjing ZHANG ; Jianting LI ; Deshun MA
Journal of Biomedical Engineering 2013;30(3):530-533
Pinch-3 protein is an important constituent of cell membranes, which directly affects the cell morphology and mechanical properties. We observed and compared the change of morphology and cell traction force of glomerular podocytes before and after Pinch-3 gene inhibition by gene interference technology in this experiment. We found that a number of pores appeared on the cell surface, and the cell projected area were increased at the same time, with an approximate average about an increase of 40% after Pinch-3 gene inhibition. The results showed that the cell traction force of glomerular podocytes was significantly reduced, with an approximate average decrease of 40%, the maximum value of the cell traction force was reduced and the distribution of cell traction force became dispersive. All this suggested that after Pinch-3 gene inhibition, some pores created on the cell surface influenced the physical properties of glomerular podocytes and then affected the cell projected area and influenced the formation and distribution of cell traction force of the glomerular podocytes as well.
Adaptor Proteins, Signal Transducing
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genetics
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physiology
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Biomechanical Phenomena
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Cell Movement
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Genetic Engineering
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Humans
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Kidney Glomerulus
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cytology
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LIM Domain Proteins
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genetics
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physiology
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Mechanotransduction, Cellular
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physiology
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Membrane Proteins
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genetics
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physiology
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Podocytes
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cytology
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physiology
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Stress, Mechanical
8.Hypermethylation of testis derived transcript gene promoter significantly correlates with worse outcomes in glioblastoma patients.
Li-jia WANG ; Yu BAI ; Zhao-shi BAO ; Yan CHEN ; Zhuo-hong YAN ; Wei ZHANG ; Quan-geng ZHANG
Chinese Medical Journal 2013;126(11):2062-2066
BACKGROUNDGlioblastoma is the most common and lethal cancer of the central nervous system. Global genomic hypomethylation and some CpG island hypermethylation are common hallmarks of these malignancies, but the effects of these methylation abnormalities on glioblastomas are still largely unclear. Methylation of the O6-methylguanine-DNA methyltransferase promoter is currently an only confirmed molecular predictor of better outcome in temozolomide treatment. To better understand the relationship between CpG island methylation status and patient outcome, this study launched DNA methylation profiles for thirty-three primary glioblastomas (pGBMs) and nine secondary glioblastomas (sGBMs) with the expectation to identify valuable prognostic and therapeutic targets.
METHODSWe evaluated the methylation status of testis derived transcript (TES) gene promoter by microarray analysis of glioblastomas and the prognostic value for TES methylation in the clinical outcome of pGBM patients. Significance analysis of microarrays was used for genes significantly differently methylated between 33 pGBM and nine sGBM. Survival curves were calculated according to the Kaplan-Meier method, and differences between curves were assessed using the log-rank test. Then, we treated glioblastoma cell lines (U87 and U251) with 5-aza-2-deoxycytidines (5-aza-dC) and detected cell biological behaviors.
RESULTSMicroarray data analysis identified TES promoter was hypermethylated in pGBMs compared with sGBMs (P < 0.05). Survival curves from the Kaplan-Meier method analysis revealed that the patients with TES hypermethylation had a short overall survival (P < 0.05). This abnormality is also confirmed in glioblastoma cell lines (U87 and U251). Treating these cells with 5-aza-dC released TES protein expression resulted in significant inhibition of cell growth (P = 0.013).
CONCLUSIONSHypermethylation of TES gene promoter highly correlated with worse outcome in pGBM patients. TES might represent a valuable prognostic marker for glioblastoma.
Azacitidine ; analogs & derivatives ; pharmacology ; Brain Neoplasms ; drug therapy ; genetics ; pathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cytoskeletal Proteins ; genetics ; DNA Methylation ; Glioblastoma ; drug therapy ; genetics ; pathology ; Humans ; LIM Domain Proteins ; genetics ; Promoter Regions, Genetic ; Treatment Outcome
9.Ribotrap analysis of proteins associated with FHL3 3'untranslated region in glioma cells.
Wei HAN ; Qing XIA ; Bin YIN ; Xiao-Zhong PENG
Chinese Medical Sciences Journal 2014;29(2):78-84
OBJECTIVETo screen the proteins associated with four-and-a-half LIM domains 3 (FHL3) 3' untranslated region (3'UTR) in glioma cells.
METHODSWestern blot was adopted to detect the regulatory effect of poly(C)-binding protein 2 (PCBP2) on FHL3. Biotin pull-down and sliver staining were employed to screen and verify the candidate binding proteins of FHL3 3'UTR. Then liquid chromatography-tandem mass spectrometry (LC-MS/MS) and molecule annotation system were used to identify and analyze the candidate binding proteins. Immuno- precipitation was conducted to study the interaction between PCBP2 and polypyrimidine tract-binding protein 1 (PTBP1), a binding protein identified by LC-MS/MS.
RESULTSPCBP2 could bind to FHL3 mRNA 3'UTR-A and inhibited the expression of FHL3 in T98G glioms cells. 22 candidate binding proteins were identified. Among them, there were 11 RNA binding proteins, including PCBP2. PTBP1 associated with FHL3 mRNA 3'UTR and interacted with PCBP2 protein.
CONCLUSIONSPCBP2 and PTBP1 can both associate with FHL3 mRNA 3'UTR through forming a protein complex.
3' Untranslated Regions ; Base Sequence ; Blotting, Western ; Brain Neoplasms ; genetics ; metabolism ; Cell Line, Tumor ; Chromatography, Liquid ; DNA Primers ; Glioma ; genetics ; metabolism ; Humans ; Intracellular Signaling Peptides and Proteins ; metabolism ; LIM Domain Proteins ; metabolism ; Neoplasm Proteins ; metabolism ; Tandem Mass Spectrometry
10.Reduced expression of PDLIM4 gene correlates with good prognosis in acute myeloid leukemia.
Yun LI ; Jun QIAN ; Jiang LIN ; Wei QIAN ; Jing YANG ; Hai-Yan CHAI ; Cui-Zhu WANG ; Zhao-Qun DENG ; Dong-Ming YAO ; Qin CHEN ; Ji-Chun MA
Journal of Experimental Hematology 2013;21(5):1111-1115
This study was aimed to investigate the expression pattern of gene PDLIM4 (PDZ and LIM domain 4) and analyze its clinical correlation with the patients suffered from acute myeloid leukemia (AML). The expression pattern of PDLIM4 in AML was detected by using EvaGreen real-time quantitative PCR (RQ-PCR). The results showed that the PDLIM4 transcript significantly decreased in 94 AML patients, compared with 21 controls (P < 0.01). The decrease of PDLIM4 transcript was found in 42 (45%) AML patients. PDLIM4 low-expression occurred among the subtypes of M1/M2/M3 more frequently than that in M4/M5/M6 (56% vs 20%, P < 0.01). AML patients with PDLIM4 low-expression had an overall survival (OS) higher than that in AML patients without PDLIM4 low-expression (P < 0.05). Analysis with receiver operating characteristic curve (ROC) displayed that PDLIM4 expression possesses the diagnostic value to differentiate AML from controls, with ROC curve area of 0.865 (95% CI: 0.801-0.930). It is concluded that reduced PDLIM4 expression is a common and favorable event for the good prognosis in AML, and can be used as a potential diagnostic biomarker of cancer.
Adolescent
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Adult
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Aged
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Biomarkers, Tumor
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metabolism
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Case-Control Studies
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DNA-Binding Proteins
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genetics
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metabolism
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Female
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Humans
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LIM Domain Proteins
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genetics
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metabolism
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Leukemia, Myeloid, Acute
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diagnosis
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genetics
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metabolism
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Male
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Middle Aged
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Prognosis
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Young Adult