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https://www.readbyqxmd.com/read/29138866/hmga2-facilitates-epithelial-mesenchymal-transition-in-renal-cell-carcinoma-by-regulating-the-tgf-%C3%AE-smad2-signaling-pathway
#1
Bo Kou, Wei Liu, Xiaoshuang Tang, Qingshan Kou
High-mobility group AT-hook 2 (HMGA2), a member of the high mobility group family, has been reported to correlate with cancer progression. However, there is no report concerning the correlation between HMGA2 and metastasis in renal cell carcinoma. In the present study, we found that HMGA2 was highly expressed in five renal cell carcinoma cell lines compared with that in the normal renal tubular epithelial HK2 cell line. Additionally, HMGA2 facilitated cell migration and invasion of renal cell carcinoma cells, as evidenced by wound healing and Transwell assays...
November 10, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29135520/epithelial-myoepithelial-carcinoma-frequent-morphologic-and-molecular-evidence-of-preexisting-pleomorphic-adenoma-common-hras-mutations-in-plag1-intact-and-hmga2-intact-cases-and-occasional-tp53-fbxw7-and-smarcb1-alterations-in-high-grade-cases
#2
Soufiane El Hallani, Aaron M Udager, Diana Bell, Isabel Fonseca, Lester D R Thompson, Adel Assaad, Abbas Agaimy, Alyssa M Luvison, Caitlyn Miller, Raja R Seethala, Simion Chiosea
We hypothesized that there is a relationship between the preexisting pleomorphic adenoma [PA]), histologic grade of epithelial-myoepithelial carcinomas (EMCAs), and genetic alterations. EMCAs (n=39) were analyzed for morphologic and molecular evidence of preexisting PA (PLAG1, HMGA2 status by fluorescence in situ hybridization, FISH, and FGFR1-PLAG1 fusion by next-generation sequencing, NGS). Twenty-three EMCAs were further analyzed by NGS for mutations and copy number variation in 50 cancer-related genes. On the basis of combined morphologic and molecular evidence of PA, the following subsets of EMCA emerged: (a) EMCAs with morphologic evidence of preexisting PA, but intact PLAG1 and HMGA2 (12/39, 31%), (b) Carcinomas with PLAG1 alterations (9/39, 23%), or (c) HMGA2 alterations (10/39, 26%), and (d) de novo carcinomas, without morphologic or molecular evidence of PA (8/39, 21%)...
November 9, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29109785/overexpression-of-mir-194-reverses-hmga2-driven-signatures-in-colorectal-cancer
#3
Hsin-Yi Chang, Shu-Ping Ye, Shiow-Lin Pan, Tzu-Ting Kuo, Bia Chia Liu, Yi-Lin Chen, Tsui-Chin Huang
Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide with increasing incidence and mortality in developed countries. Oncogenes and microRNAs regulate key signaling pathways in CRC and are known to be deregulated. Oncogenic transcriptional regulator high-mobility group AT-hook 2 (HMGA2) participates in the transformation of several cancers including CRC and exhibits strong correlation with poor prognosis and distal metastasis. Evidence of HMGA2 and its co-regulated miRs contributing to tumor progression remains to be clarified...
2017: Theranostics
https://www.readbyqxmd.com/read/29079814/the-role-of-thyroid-transcription-factor-1-and-tumor-differentiation-in-resected-lung-adenocarcinoma
#4
Tsai-Wang Huang, Ke- Feng Lin, Chien-Hsing Lee, Hung Chang, Shih-Chun Lee, Yi-Shing Shieh
To investigate the role of thyroid transcription factor-1 (TTF-1) and tumor differentiation in resected lung adenocarcinoma. A total of 520 patients with clinical early stage lung adenocarcinoma who underwent surgical resection were reviewed retrospectively. Clinical data and outcomes were evaluated with an average follow-up of 117 months. The results were validated via lung cancer cell line studies. The clinical parameters did not differ between relapse and nonrelapse patients. Exceptions were tumor differentiation, lymphovascular space invasion, F(18)-fluorodeoxyglucose maximum standard uptake value, tumor size, and pathological stage (p < 0...
October 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29073636/global-metabolomic-profiling-of-uterine-leiomyomas
#5
Hanna-Riikka Heinonen, Miika Mehine, Netta Mäkinen, Annukka Pasanen, Esa Pitkänen, Auli Karhu, Nanna S Sarvilinna, Jari Sjöberg, Oskari Heikinheimo, Ralf Bützow, Lauri A Aaltonen, Eevi Kaasinen
BACKGROUND: Uterine leiomyomas can be classified into molecularly distinct subtypes according to their genetic triggers: MED12 mutations, HMGA2 upregulation, or inactivation of FH. The aim of this study was to identify metabolites and metabolic pathways that are dysregulated in different subtypes of leiomyomas. METHODS: We performed global metabolomic profiling of 25 uterine leiomyomas and 17 corresponding myometrium specimens using liquid chromatography-tandem mass spectroscopy...
October 26, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29066347/jak2v617f-influences-epigenomic-changes-in-myeloproliferative-neoplasms
#6
Chih-Cheng Chen, Chia-Chen Chiu, Kuan-Der Lee, Chia-Chen Hsu, Hong-Chi Chen, Tim H-M Huang, Shu-Huei Hsiao, Yu-Wei Leu
Negative valine (V) to phenylalanine (F) switch at the Janus kinase (JAK2) 617 codon (V617F) is the dominant driver mutation in patients with myeloproliferative neoplasms (MPNs). JAK2V617F was proved to be sufficient for cell transformation; however, independent mutations might influence the following epigenomic modifications. To assess the JAK2V617F-induced downstream epigenomic changes without interferences, we profiled the epigenomic changes in ectopically expressed JAK2V617F in Ba/F3 cells. Antibodies against phosphorylated signal transducer and activator of transcription 3 (pSTAT3) and enhancer of zeste homolog 2 (EZH2) were used for chromatin-immunoprecipitation sequencing (ChIP-seq) to detect the downstream epigenomic targets in the JAK2-STAT3 signaling pathway...
October 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29059722/genome-wide-association-study-reveals-genetic-loci-and-candidate-genes-for-average-daily-gain-in-duroc-pigs
#7
Jianping Quan, Rongrong Ding, Xingwang Wang, Ming Yang, Yang Yang, Enqin Zheng, Ting Gu, Gengyuan Cai, Zhenfang Wu, Dewu Liu, Jie Yang
Objective: Average daily gain (ADG) is an important target trait of pig breeding programs. We aimed to identify single nucleotide polymorphisms (SNPs) and genomic regions that are associated with ADG in the Duroc pig population. Methods: We performed a genome-wide association study involving 390 Duroc boars and by using the PorcineSNP60K Beadchip and two linear models. Results: After quality control, we detected 35971 SNPs, which included seven SNPs that are significantly associated with the ADG of pigs...
October 20, 2017: Asian-Australasian Journal of Animal Sciences
https://www.readbyqxmd.com/read/29055020/subtype-specific-tumor-associated-fibroblasts-contribute-to-the-pathogenesis-of-uterine-leiomyoma
#8
Xin Wu, Vanida Ann Serna, Justin Thomas, Wenan Qiang, Michael L Blumenfeld, Takeshi Kurita
Recent genomic studies have identified subtypes of uterine leiomyoma (LM) with distinctive genetic alterations. Here we report the elucidation of the biological characteristics of the two most prevalent LM subtypes, MED12 mutant (MED12-LM) and HMGA2-overexpressing (HMGA2-LM) LM. Since each tumor carries only one genetic alteration, both subtypes are considered to be monoclonal. Approximately 90% of cells in HMGA2-LM were smooth muscle cells (SMC) with HMGA2 overexpression. In contrast, MED12-LM consisted of similar numbers of SMC and non-SMC, which were mostly tumor-associated fibroblasts (TAF)...
October 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/29033353/melanocyte-stem-cell-activation-and-translocation-initiate-cutaneous-melanoma-in-response-to-uv-exposure
#9
Hyeongsun Moon, Leanne R Donahue, Eunju Choi, Philip O Scumpia, William E Lowry, Jennifer K Grenier, Jerry Zhu, Andrew C White
Melanoma is one of the deadliest cancers, yet the cells of origin and mechanisms of tumor initiation remain unclear. The majority of melanomas emerge from clear skin without a precursor lesion, but it is unknown whether these melanomas can arise from melanocyte stem cells (MCSCs). Here we employ mouse models to define the role of MCSCs as melanoma cells of origin, demonstrate that MCSC quiescence acts as a tumor suppressor, and identify the extrinsic environmental and molecular factors required for the critical early steps of melanoma initiation...
November 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29031931/global-analysis-of-ago2-bound-rnas-reveals-that-mirnas-induce-cleavage-of-target-rnas-with-limited-complementarity
#10
Eunsun Jung, Youngmo Seong, Bohyun Jeon, Hoseok Song, Young-Soo Kwon
Among the four Argonaute family members in mammals, only AGO2 protein retains endonuclease activity and facilitates cleavage of target RNAs base-pairing with highly complementary guide RNAs. Despite the deeply conserved catalytic activity, only a small number of targets have been reported to extensively base pair with cognate miRNAs to be cleaved by AGO2. Here, we analyzed AGO2-bound RNAs by CrossLinking ImmunoPrecipitation (CLIP) of genetically modified cells that express epitope-tagged AGO2 from the native genomic locus...
November 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29025583/a-rare-case-of-pediatric-lipoma-with-t-9-12-p22-q14-and-evidence-of-hmga2-nfib-gene-fusion
#11
Melanie Lacaria, Dina El Demellawy, Jean McGowan-Jordan
Lipoma is a benign tumor, typically of adulthood, with characteristic cytogenetic findings, including rearrangement of 12q13-15; these rearrangements often lead to the fusion of the HMGA2 gene at this locus to the transcriptional regulatory domain of its fusion partner, resulting in neomorphic activity that presumably facilitates the neoplastic process. Herein, we report a rare case of pediatric lipoma with t(9;12)(p22;q14) and evidence of HMGA2-NFIB gene fusion in a 9 year-old boy. This case provides further evidence of the link between NFIB rearrangement and early-onset, deep-seated lipomatous tumors...
October 2017: Cancer Genetics
https://www.readbyqxmd.com/read/29025376/roles-of-microrna-let-7b-in-papillary-thyroid-carcinoma-by-regulating-hmga2
#12
Hongguang Li, Lihong Zhao, Zhenhua Zhang, Heng Zhang, Chao Ding, Zijie Su
The incidence of thyroid cancer has increased significantly in the last decade, and the most frequent type of this cancer is papillary thyroid carcinoma. MicroRNAs have been demonstrated to be abnormally expressed in tumors and associated with the development of the tumors. Our aim was to analyze the role and molecular mechanisms of tumor suppressor let-7b in the papillary thyroid carcinoma. Expression of let-7b and high-mobility group A2 in papillary thyroid carcinoma tissues and cell lines was assessed using quantitative reverse transcription polymerase chain reaction and western blot analysis...
October 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/29017393/expression-of-hsa-let-7b-5p-hsa-let-7f-5p-and-hsa-mir-222-3p-and-their-putative-targets-hmga2-and-cdkn1b-in-typical-and-atypical-carcinoid-tumors-of-the-lung
#13
Pietro Di Fazio, Moritz Maass, Silvia Roth, Christian Meyer, Joana Grups, Peter Rexin, Detlef K Bartsch, Andreas Kirschbaum
Typical and atypical carcinoid tumors belong to the neuroendocrine lung tumors. They have low recurrence and proliferation rate, lymph node, and distant metastases. Nevertheless, these tumors have shown a more aggressive behavior. In the last years, microRNAs were screened as new tumor markers for their potential diagnostic and therapeutic relevance. The expression of hsa-let-7b-5p, hsa-let-7f-5p, hsa-miR-222-3p, and their targets HMGA2 (high-mobility group A2) and CDKN1B (cyclin-dependent kynase inhibitor 1B, p27(kip1)) was evaluated in this rare small group of patients...
October 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28985345/replication-stress-induced-endogenous-dna-damage-drives-cellular-senescence-induced-by-a-sub-lethal-oxidative-stress
#14
Gireedhar Venkatachalam, Uttam Surana, Marie-Véronique Clément
Although oxidative stress has been shown to induce senescence and replication stress independently, no study has implicated unresolved replication stress as the driver for cellular senescence in response to oxidative stress. Using cells exposed to increasing concentrations of hydrogen peroxide, we show that sub-lethal amount of exogenous hydrogen peroxide induces two waves of DNA damage. The first wave is rapid and transient while the second wave coincides with the cells transition from the S to the G2/M phases of cell cycle...
October 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28976449/a-2-protein-signature-predicting-clinical-outcome-in-high-grade-serous-ovarian-cancer
#15
Chengjuan Jin, Yingfeng Xue, Yingwei Li, Hualei Bu, Hongfeng Yu, Tao Zhang, Zhiwei Zhang, Shi Yan, Nan Lu, Beihua Kong
OBJECTIVE: High-grade serous ovarian cancer (HGSOC) accounts for approximately 70% deaths in ovarian cancer. The overall survival (OS) of HGSOC is poor and still remains a clinical challenge. High-grade serous ovarian cancer can be divided into 4 molecular subtypes. The prognosis of different molecular subtypes is still unclear. We aimed to investigate the prognostic values of immunohistochemistry-based different molecular subtypes in patients with HGSOC. METHODS: We analyzed the protein expression of representative biomarkers (CXCL11, HMGA2, and MUC16) of 3 different molecular subtypes in 110 formalin-fixed, paraffin-embedded HGSOC by tissue microarrays...
October 3, 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/28968424/mir-125b-5p-functions-as-a-tumor-suppressor-gene-partially-by-regulating-hmga2-in-esophageal-squamous-cell-carcinoma
#16
Li-Li Mei, Wen-Jun Wang, Yun-Tan Qiu, Xiu-Feng Xie, Jie Bai, Zhi-Zhou Shi
MicroRNAs (miRNAs) play important roles in the progression of human cancer including esophageal squamous cell carcinoma (ESCC). Although previous reports showed that miR-125b-5p was down-regulated in ESCC, the roles and mechanisms of loss of function of miR-125b-5p in ESCC were still unknown. Using microRNA microarray and GEO datasets, we found and confirmed that miR-125b-5p was down-regulated in ESCC tissues. In-vitro assays showed that ectopic miR-125b-5p expression repressed cell proliferation, migration and invasion, and induced cell senescence...
2017: PloS One
https://www.readbyqxmd.com/read/28963864/microrna-495-inhibits-new-bone-regeneration-via-targeting-high-mobility-group-at-hook-2-hmga2
#17
Zhao Tian, Haizhen Zhou, Yuben Xu, Jie Bai
BACKGROUND MicroRNAs play critical roles in post-translational gene expression. In this study, we explored the role of miR-495 in new bone regeneration. MATERIAL AND METHODS Murine calvarial osteoblasts were isolated and cultured. Microarray was performed to identify differential miRNAs in medicarpin-induced osteoblasts differentiation. Luciferase reporter assay was performed to identify the target gene of miRNA. Murine osteoblast cells were transfected with miC, miR-495, or anti-miR-495. CCK-8 and flow cytometry were performed to detect osteoblasts proliferation and apoptosis...
September 30, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28954272/cxcr4-let-7a-axis-regulates-metastasis-and-chemoresistance-of-pancreatic-cancer-cells-through-targeting-hmga2
#18
Guangfa Xiao, Xitao Wang, Yaqun Yu
BACKGROUND/AIMS: Pancreatic cancer cells (PCC) is one of the most risky cancers and gemcitabine (GEM) is the standard first-line drug for treating PCC. The PCC will develop drug resistance to GEM after a period of treatment. However, the detailed molecular mechanism of pathogenesis and drug resistance remains unresolved. METHODS: we employed qRT-PCR and western blot to examine the expression level of CXCR4, let-7a and HMGA2. In addition, we used MTT assay to detect cell proliferation and transwell assay to measure migration and invasiveness...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28948632/circulating-cell-free-high-mobility-group-at-hook-2-mrna-as-a-detection-marker-in-the-serum-of-colorectal-cancer-patients
#19
Sana Sahengbieke, Jian Wang, Xiangwei Li, Yuhong Wang, Maode Lai, Jingjing Wu
BACKGROUND: Detection of circulating cell-free mRNA serves as noninvasive tools for cancer diagnosis. As an oncofetal protein, HMGA2 (high mobility group AT-hook 2) is upregulated in colorectal cancer (CRC) tissues. However, it is not clear whether the increased levels of circulating cell-free HMGA2 mRNA functions as potential biomarkers for improved diagnosis of CRC. METHODS: To assess its clinical significance in diagnosis and prediction, we evaluated serum levels of circulating HMGA2 mRNA in CRC patients and in healthy controls...
September 26, 2017: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/28947981/lin28b-facilitates-the-progression-and-metastasis-of-pancreatic-ductal-adenocarcinoma
#20
Yunchao Wang, Jian Li, Shixiang Guo, Yongsheng Ouyang, Liangyu Yin, Songsong Liu, Zhiping Zhao, Jiali Yang, Wenjie Huang, Huan Qin, Xin Zhao, Bing Ni, Huaizhi Wang
Lin28B, a Lin28 homologue, represses the biogenesis of let-7 microRNAs (miRNAs), has a role in tumorigenesis, and is considered a potential therapeutic target for various human malignancies. However, the associations between Lin28B and the clinical features and outcomes of patients with pancreatic ductal adenocarcinoma (PDAC) remain unclear. In this study, we explored the clinical significance of Lin28B in PDAC and its association with metastasis by examining tissues from patients with PDAC and elucidated the molecular mechanisms using PDAC cell lines...
September 1, 2017: Oncotarget
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