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HMGA2

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https://www.readbyqxmd.com/read/28057739/aberrant-let7a-hmga2-signaling-activity-with-unique-clinical-phenotype-in-jak2-mutated-myeloproliferative-neoplasms
#1
Chih-Cheng Chen, Jie-Yu You, Jrhau Lung, Cih-En Huang, Yi-Yang Chen, Yu-Wei Leu, Hsing-Ying Ho, Chian-Pei Li, Chang-Hsien Lu, Kuan-Der Lee, Chia-Chen Hsu, Jyh-Pyng Gau
High mobility group AT-hook 2 (HMGA2) is an architectural transcriptional factor that is negatively regulated by Let-7 microRNA through binding to its 3-untranslated region (3-UTR). Transgenic mice expressing HMGA2 with a truncation of its 3-UTR has been shown to exhibit a myeloproliferative phenotype. To decipher the Let-7-HMGA2 axis in myeloproliferative neoplasms (MPN), we employed an in vitro model supplemented with clinical correlation. Ba/F3 cells with inducible JAK2V617F expression (Ton.JAK2.V617F cells) showed up-regulation of HMGA2 with concurrent let-7a repression...
January 5, 2017: Haematologica
https://www.readbyqxmd.com/read/27986804/dwarfism-and-altered-craniofacial-development-in-rabbits-is-caused-by-a-12-1-kb-deletion-at-the-hmga2-locus
#2
Miguel Carneiro, Dou Hu, John Archer, Chungang Feng, Sandra Afonso, Congying Chen, José A Blanco-Aguiar, Hervé Garreau, Samuel Boucher, Paula G Ferreira, Nuno Ferrand, Carl-Johan Rubin, Leif Andersson
The dwarf phenotype characterizes the smallest of rabbit breeds and is governed largely by the effects of a single dwarfing allele with an incompletely dominant effect on growth. Dwarf rabbits typically weigh under 1 kg and have altered craniofacial morphology. The dwarf allele is a recessive lethal and dwarf homozygotes die within a few days of birth. The dwarf phenotype is expressed in heterozygous individuals and rabbits from dwarf breeds homozygous for the wild-type allele are normal, although smaller when compared to other breeds...
December 16, 2016: Genetics
https://www.readbyqxmd.com/read/27956228/genome-wide-crispr-screen-identifies-regulators-of-mapk-as-suppressors-of-liver-tumors-in-mice
#3
Chun-Qing Song, Yingxiang Li, Haiwei Mou, Jill Moore, Angela Park, Yotsawat Pomyen, Soren Hough, Zachary Kennedy, Andrew Fischer, Hao Yin, Daniel G Anderson, Darryl Conte, Lars Zender, Xin Wei Wang, Snorri Thorgeirsson, Zhiping Weng, Wen Xue
BACKGROUND & AIMS: It has been a challenge to identify liver tumor suppressors or oncogenes due to the genetic heterogeneity of these tumors. We performed a genome-wide screen to identify suppressors of liver tumor formation in mice, using CRISPR-mediated genome editing. METHODS: We performed a genome-wide CRISPR/Cas9-based knockout screen of P53-null mouse embryonic liver progenitor cells that overexpressed MYC. We infected p53(-/-);Myc;Cas9 hepatocytes with the mGeCKOa lentiviral library of 67,000 single-guide RNAs (sgRNAs), targeting 20,611 mouse genes, and transplanted the transduced cells subcutaneously into nude mice...
December 9, 2016: Gastroenterology
https://www.readbyqxmd.com/read/27940362/stat3-stimulates-adipogenic-stem-cell-proliferation-and-cooperates-with-hmga2-during-the-early-stage-of-differentiation-to-promote-adipogenesis
#4
Yanyan Yuan, Yang Xi, Jiayi Chen, Pan Zhu, Jinyu Kang, Zuquan Zou, Fuyan Wang, Shizhong Bu
Signal transducer and activator of transcription 3 (STAT3) is abundantly expressed in the adipose tissue of obese mice and humans, but the role of STAT3 in adipogenesis is still not fully understood. In the present study, we discovered an activation of STAT3 during the early differentiation stage of mouse 3T3-L1 preadipocytes. Stat3 knockdown using siRNA blocked cell cycle progression of both preadipoctes and early differentiating cells. Moreover, accumulation of lipid droplets was inhibited by Stat3 knockdown...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27932890/high-expression-of-hmga2-predicts-poor-survival-in-patients-with-clear-cell-renal-cell-carcinoma
#5
Ning Na, Tujie Si, Zhengyu Huang, Bin Miao, Liangqing Hong, Heng Li, Jiang Qiu, Jianguang Qiu
High-mobility group AT-hook 2 (HMGA2) is involved in a wide spectrum of biological processes and is upregulated in several tumors, but its role in renal carcinoma remains unclear. The aim of this study was to examine the expression of HMGA2 and its relationship to the overall survival (OS) of patients with non-metastatic clear cell renal cell carcinoma (ccRCC) following surgery. The expression of HMGA2 was evaluated retrospectively by immunohistochemistry (IHC) in 162 patients with ccRCC who underwent nephrectomy in 2003 and 2004...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27929737/long-noncoding-rna-hit000218960-promotes-papillary-thyroid-cancer-oncogenesis-and-tumor-progression-by-upregulating-the-expression-of-high-mobility-group-at-hook-2-hmga2-gene
#6
Tao Li, Xiao-Dong Yang, Chun-Xiang Ye, Zhan-Long Shen, Yang Yang, Bo Wang, Peng Guo, Zhi-Dong Gao, Ying-Jiang Ye, Ke-Wei Jiang, Shan Wang
Accumulating evidence suggests that long noncoding RNAs (lncRNAs) play an important role in oncogenesis and tumor progression. However, our knowledge of lncRNAs in thyroid cancer is still limited. To explore the crucial lncRNAs involved in oncogenesis of papillary thyroid cancer (PTC), we acquired data of differentially expressed lncRNAs between PTC tissues and paired adjacent noncancerous thyroid tissues through lncRNA microarray. In the microarray data, we observed that a newly identified lncRNA, HIT000218960, was significantly upregulated in PTC tissues and associated with a well-known oncogene, high mobility group AT-hook 2 (HMGA2) gene...
December 8, 2016: Cell Cycle
https://www.readbyqxmd.com/read/27928058/identification-of-senescence-associated-circular-rnas-sac-rnas-reveals-senescence-suppressor-circpvt1
#7
Amaresh C Panda, Ioannis Grammatikakis, Kyoung Mi Kim, Supriyo De, Jennifer L Martindale, Rachel Munk, Xiaoling Yang, Kotb Abdelmohsen, Myriam Gorospe
Using RNA sequencing (RNA-Seq), we compared the expression patterns of circular RNAs in proliferating (early-passage) and senescent (late-passage) human diploid WI-38 fibroblasts. Among the differentially expressed senescence-associated circRNAs (which we termed 'SAC-RNAs'), we identified CircPVT1, generated by circularization of an exon of the PVT1 gene, as a circular RNA showing markedly reduced levels in senescent fibroblasts. Reducing CircPVT1 levels in proliferating fibroblasts triggered senescence, as determined by a rise in senescence-associated β-galactosidase activity, higher abundance of CDKN1A/P21 and TP53, and reduced cell proliferation...
December 7, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27920151/lin28-is-induced-in-primed-embryonic-stem-cells-and-regulates-let-7-independent-events
#8
Silvia Parisi, Fabiana Passaro, Luigi Russo, Anna Musto, Angelica Navarra, Simona Romano, Giuseppe Petrosino, Tommaso Russo
Lin28 RNA-binding proteins play important roles in pluripotent stem cells, but the regulation of their expression and the mechanisms underlying their functions are still not definitively understood. Here we address the above-mentioned issues in the first steps of mouse embryonic stem cell (ESC) differentiation. We observed that the expression of Lin28 genes is transiently induced soon after the exit of ESCs from the naive ground state and that this induction is due to the Hmga2-dependent engagement of Otx2 with enhancers present at both Lin28 gene loci...
December 5, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27917442/polymorphisms-in-ten-candidate-genes-are-associated-with-conformational-and-locomotive-traits-in-spanish-purebred-horses
#9
Natalia Sevane, Susana Dunner, Ana Boado, Javier Cañon
The Spanish Purebred horses, also known as Andalusian horses, compete to the highest standards in international dressage events. Gait and conformation could be used as early selection criteria to detect young horses with promising dressage ability. Although the genetic background of equine size variation has been recently uncovered, the genetic basis of horse conformational and locomotive traits is not known, hampered by the complex genetic architecture underlying quantitative traits and the lack of phenotypic data...
December 5, 2016: Journal of Applied Genetics
https://www.readbyqxmd.com/read/27878307/hmga2-regulates-epithelial-mesenchymal-transition-and-the-acquisition-of-tumor-stem-cell-properties-through-twist1-in-gastric-cancer
#10
Wei Li, Ziwei Wang, Lang Zha, Dequan Kong, Gang Liao, Hui Li
High expression of high mobility group protein A2 (HMGA2) is correlated with the invasiveness of gastric cancer and is an independent prognostic factor. The reason may be that HMGA2 promotes epithelial-mesenchymal transition (EMT) and the acquisition of tumor stem cell properties, yet the mechanism remains unclear. In this study, immunohistochemistry and western blot analysis revealed that the expression of HMGA2 and Twist-related protein 1 (TWIST1) in gastric carcinoma tissues was higher than that in the peritumoral tissues and that the expression levels of these two proteins were positively correlated...
January 2017: Oncology Reports
https://www.readbyqxmd.com/read/27876874/twist1-drives-cisplatin-resistance-and-cell-survival-in-an-ovarian-cancer-model-via-upregulation-of-gas6-l1cam-and-akt-signalling
#11
Cai M Roberts, Michelle A Tran, Mary C Pitruzzello, Wei Wen, Joana Loeza, Thanh H Dellinger, Gil Mor, Carlotta A Glackin
Epithelial ovarian cancer (EOC) is the most deadly gynaecologic malignancy due to late onset of symptoms and propensity towards drug resistance. Epithelial-mesenchymal transition (EMT) has been linked to the development of chemoresistance in other cancers, yet little is known regarding its role in EOC. In this study, we sought to determine the role of the transcription factor TWIST1, a master regulator of EMT, on cisplatin resistance in an EOC model. We created two Ovcar8-derived cell lines that differed only in their TWIST1 expression...
November 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27874955/expression-and-significances-of-mirna-let-7-and-hmga2-in-laryngeal-carcinoma
#12
F-C Song, Y Yang, J-X Liu
OBJECTIVE: High mobility group protein A2 (HMGA2) is a reported new oncogene been regulated by tumor suppressor microRNA Let-7. HMGA2 has become a hot topic in fundamental and clinical research of laryngeal carcinoma. The aim of the current study is to investigate the molecular mechanism of Let-7 and HMGA2 in oncogenesis and progression of laryngeal cancer. PATIENTS AND METHODS: We used quantitative RT-PCR to detect the expression of miRNA Let-7a and HMGA2 mRNA from 59 pairs of fresh laryngeal cancer tissues and adjacent tissues collected for the laryngeal cancer patient...
November 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27861570/hmga2-moderately-increases-fetal-hemoglobin-expression-in-human-adult-erythroblasts
#13
Jaira F de Vasconcellos, Y Terry Lee, Colleen Byrnes, Laxminath Tumburu, Antoinette Rabel, Jeffery L Miller
Induction of fetal hemoglobin (HbF) has therapeutic importance for patients with beta-hemoglobin disorders. Previous studies showed that let-7 microRNAs (miRNAs) are highly regulated in erythroid cells during the fetal-to-adult developmental transition, and that targeting let-7 mediated the up-regulation of HbF to greater than 30% of the total globin levels in human adult cultured erythroblasts. HMGA2 is a member of the high-mobility group A family of proteins and a validated target of the let-7 family of miRNAs...
2016: PloS One
https://www.readbyqxmd.com/read/27843907/targeting-hmga2-in-retinoblastoma-cells-in-vitro-using-the-aptamer-strategy
#14
Venkatesan Nalini, Perinkulam Ravi Deepa, Rajeswari Raguraman, Vikas Khetan, Maddy Ashwin Reddy, Subramanian Krishnakumar
High-mobility group A2 (HMGA2) protein regulates retinoblastoma (RB) cancer cell proliferation. Here, a stable phosphorothioate-modified HMGA2 aptamer was used to block HMGA2 protein function in RB cells. HMGA2-aptamer internalisation in RB cells (Y79, Weri Rb1) and non-neoplastic human retinal cells (MIO-M1) were optimised. Aptamer induced dose-dependent cytotoxicity in RB cancer cells (0.25-1.5 µM). Increased expression of TGFβ, SMAD4, CDH1, BAX, CASP 3, PARP mRNA and decreased SNAI1, Bcl2 mRNA levels in aptamer-treated RB cells suggests the activation of TGFβ-SMAD4-mediated apoptotic pathway...
October 2016: Ocular Oncology and Pathology
https://www.readbyqxmd.com/read/27835588/expressions-of-mir-30c-and-let-7a-are-inversely-correlated-with-hmga2-expression-in-squamous-cell-carcinoma-of-the-vulva
#15
Antonio Agostini, Marta Brunetti, Ben Davidson, Claes G Trope, Sverre Heim, Ioannis Panagopoulos, Francesca Micci
Malignant tumors of the vulva, most of them squamous cell carcinomas, account for only 5% of cancers of the female genital tract. Though little is known about the genetic features of these tumors, the Fragile Histidine Triad (FHIT) and High Mobility Group AT-hook 2 (HMGA2) genes were found deregulated. We wanted to gain more knowledge about the expression of HMGA2-related miRNAs such as miR-30c and let-7a, and whether a correlation exists between the expression of FHIT and HMGA2, in this tumor type. An inverse correlation was found in-as-much as HMGA2 was highly expressed (mean fold change 8...
November 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27830017/ccat1-promotes-laryngeal-squamous-cell-carcinoma-cell-proliferation-and-invasion
#16
Kun Zhuang, Qiang Wu, Senhe Jiang, Huijun Yuan, Shaomin Huang, Huijun Li
Long noncoding RNAs (lncRNAs) are proved tobe deregulated in a number of cancers and play important roles in tumor biology. Colon cancer-associated transcript-1 (CCAT1) was initially found in colon cancer and promoted cancer cell development. However, the role of CCAT1 in laryngeal squamous cell carcinoma (LSCC) is still unknown. In this study, we demonstrated that CCAT1 expression was upregulated in the LSCC tissues compared with the normal adjacent tissues. Moreover, CCAT1 expression was higher in LSCC tissues thanin adjacent normal tissues in 70% of patients...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27821801/trim71-suppresses-tumorigenesis-via-modulation-of-lin28b-let-7-hmga2-signaling
#17
Jinlong Yin, Tae-Hoon Kim, Nayun Park, Daye Shin, Hae In Choi, Sungchan Cho, Jong Bae Park, Jong Heon Kim
TRIM71 (tripartite motif-containing 71) belongs to the TRIM-NHL protein family, which plays a conserved role in regulating early development and differentiation. However, the molecular functions of TRIM71 have remained largely unknown. Here, we explored the role of TRIM71 together with modulation of Lin28B-let-7-HMGA2 (high-mobility group AT-hook 2) signaling in tumorigenesis. TRIM71 overexpression opposed Lin28B-induced transformation in primary cells and inhibited tumor formation in a mouse model. Specific knockdown of TRIM71 expression increased cancer cell proliferation and invasion...
November 3, 2016: Oncotarget
https://www.readbyqxmd.com/read/27821050/stringent-comparative-sequence-analysis-reveals-sox10-as-a-putative-inhibitor-of-glial-cell-differentiation
#18
Chetna Gopinath, William D Law, José F Rodríguez-Molina, Arjun B Prasad, Lingyun Song, Gregory E Crawford, James C Mullikin, John Svaren, Anthony Antonellis
BACKGROUND: The transcription factor SOX10 is essential for all stages of Schwann cell development including myelination. SOX10 cooperates with other transcription factors to activate the expression of key myelin genes in Schwann cells and is therefore a context-dependent, pro-myelination transcription factor. As such, the identification of genes regulated by SOX10 will provide insight into Schwann cell biology and related diseases. While genome-wide studies have successfully revealed SOX10 target genes, these efforts mainly focused on myelinating stages of Schwann cell development...
November 7, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27809392/hmga2-is-associated-with-the-aggressiveness-of-tongue-squamous-cell-carcinoma
#19
H Zhang, Z Tang, C Deng, Y He, F Wu, O Liu, C Hu
OBJECTIVE: To analyze the effects of HMGA2 on proliferation, invasion, and metastasis in tongue squamous cell carcinoma (TSCC). METHODS: HMGA2 knockdown was performed in SCC15 cell lines, and functional assay was applied to observe the effects on cell migration and invasion. Real-time PCR, Western blotting, and immunohistochemistry (IHC) were also used to measure the expression of HMGA2 and EMT markers. RESULTS: HMGA2 expression was decreased after lentivirus infection...
November 3, 2016: Oral Diseases
https://www.readbyqxmd.com/read/27793213/a-panel-of-four-genes-accurately-differentiates-benign-from-malignant-thyroid-nodules
#20
Qing-Xuan Wang, En-Dong Chen, Ye-Feng Cai, Quan Li, Yi-Xiang Jin, Wen-Xu Jin, Ying-Hao Wang, Zhou-Ci Zheng, Lu Xue, Ou-Chen Wang, Xiao-Hua Zhang
BACKGROUND: Clinicians are confronted with an increasing number of patients with thyroid nodules. Reliable preoperative diagnosis of thyroid nodules remains a challenge because of inconclusive cytological examination of fine-needle aspiration biopsies. Although molecular analysis of thyroid tissue has shown promise as a diagnostic tool in recent years, it has not been successfully applied in routine clinical use, particularly in Chinese patients. METHODS: Whole-transcriptome sequencing of 19 primary papillary thyroid cancer (PTC) samples and matched adjacent normal thyroid tissue (NT) samples were performed...
October 28, 2016: Journal of Experimental & Clinical Cancer Research: CR
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