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Jason W Hoskins, Abdisamad Ibrahim, Mickey A Emmanuel, Sarah M Manmiller, Yinglun Wu, Maura O'Neill, Jinping Jia, Irene Collins, Mingfeng Zhang, Janelle V Thomas, Lauren M Rost, Sudipto Das, Hemang Parikh, Jefferson M Haake, Gail L Matters, Robert C Kurtz, William R Bamlet, Alison Klein, Rachael Stolzenberg-Solomon, Brian M Wolpin, Ronit Yarden, Zhaoming Wang, Jill Smith, Sara H Olson, Thorkell Andresson, Gloria M Petersen, Laufey T Amundadottir
Genome-wide association studies (GWAS) have identified multiple common susceptibility loci for pancreatic cancer. Here we report fine-mapping and functional analysis of one such locus residing in a 610 kb gene desert on chr13q22.1 (marked by rs9543325). The closest candidate genes, KLF5, KLF12, PIBF1, DIS3 and BORA, range in distance from 265-586 kb. Sequencing three sub-regions containing the top ranked SNPs by imputation P-value revealed a 30 bp insertion/deletion (indel) variant that was significantly associated with pancreatic cancer risk (rs386772267, P = 2...
August 30, 2016: Human Molecular Genetics
Shuai-Shuai Zhang, Yan Xu, Shu-Hui Deng, Chang-Hong Li, Wen Zhou, Lu-Gui Qiu
UNLABELLED: Objectiive:To explore the effect of miR137 target gene MITF on the prognosis of multiple myeloma (MM). METHODS: The target genes of miR137 were predicted by software, the GFP analysis was carried out for detecting MITF as the prognosis of multiple myeloma. The cell line overexpressing miR137 in MM cell line was constructed. Real-time qPCR and Western blot were used to detect the expression of MITF in this cell line. RESULTS: The target genes of miR137 were MITF, BUE2H, SH3BP5 and KLF12...
August 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
Yantao Du, Yichen Chen, Furong Wang, Liankun Gu
Aberrant expression of miR-137 has been reported in many kinds of cancers, but its mechanisms seem to be diversely. In the present study, we compared the expression level of miR-137 in 18 paired gastric cancer (GC) samples and surgical margin (SM) samples by RNA extraction and quantitative real-time PCR (QRT-PCR). Then, we investigated the effects of miR-137 on cell proliferation, cell cycle, and cell migration separately by cell growth counting assay, cell cycle analysis, and transwell assay. Candidate targets of miR-137 were selected by biological information analysis from the intersection of miRDB, Pictar, and TarScan...
July 28, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
B Guan, Q Li, X H Li, X J Zhou
OBJECTIVE: To identify basal-like breast carcinoma (BLBC)-specific microRNA (miRs) and its target gene and to investigate the distinct biological function. METHOD: Krüppel-like factor 12 (KLF12) 3'-UTR was constructed and luciferase reporter assay was performed for target gene. Expression levels of miR including its target genes were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR), Western blot and immunohistochemistry (IHC). Further functional analyses were conducted which included apoptosis...
July 12, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Sun-Hee Kim, Yun-Yong Park, Sung-Nam Cho, Ofer Margalit, Dingzhi Wang, Raymond N DuBois
Krüppel-like factor 12 (KLF12) is a transcription factor that plays a role in normal kidney development and repression of decidualization. KLF12 is frequently elevated in esophageal adenocarcinoma and has been reported to promote gastric cancer progression. Here, we examined the role of KLF12 in colorectal cancer (CRC). Indeed, KLF12 promotes tumor growth by directly activating early growth response protein 1 (EGR1). The levels of KLF12 and EGR1 correlate synergistically with a poor prognosis. These results indicate that KLF12 likely plays an important role in CRC and could serve as a potential prognostic marker and therapeutic target...
2016: PloS One
H-Q Zhou, Q-C Chen, Z-T Qiu, W-L Tan, C-Q Mo, S-W Gao
OBJECTIVE: Pancreatic neuroendocrine tumors are relatively rare pancreatic neoplasms over the world. Investigations of the molecular biology of PNETs are insufficient for nowadays. We aimed to explore the expression of microRNA and messenger RNA and regulatory processes underlying pancreatic neuroendocrine tumors. MATERIALS AND METHODS: The messenger RNA and microRNA expression profile of GSE43796 were downloaded, including 6 samples with pancreatic neuroendocrine tumors and 5 healthy samples...
July 2016: European Review for Medical and Pharmacological Sciences
Bing Guan, Qing Li, Li Shen, Qiu Rao, Yan Wang, Yun Zhu, Xiao-Jun Zhou, Xiao-Hong Li
We investigated microRNAs (miRs) specific to its target gene and exerting distinct biological functions for basal-like breast carcinoma (BLBC). Total RNA was extracted and subjected to miR microarray and bioinformatics analysis. Based on the comprehensive analysis, expression of miRs including its target was analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blot analysis and immunohistochemistry (IHC). Further functional analyses were conducted including proliferation, invasion and apoptosis...
August 2016: International Journal of Oncology
Yong-Biao Zhang, Jintian Hu, Jiao Zhang, Xu Zhou, Xin Li, Chaohao Gu, Tun Liu, Yangchun Xie, Jiqiang Liu, Mingliang Gu, Panpan Wang, Tingting Wu, Jin Qian, Yue Wang, Xiaoqun Dong, Jun Yu, Qingguo Zhang
Craniofacial microsomia (CFM) is a rare congenital anomaly that involves immature derivatives from the first and second pharyngeal arches. The genetic pathogenesis of CFM is still unclear. Here we interrogate 0.9 million genetic variants in 939 CFM cases and 2,012 controls from China. After genotyping of an additional 443 cases and 1,669 controls, we identify 8 significantly associated loci with the most significant SNP rs13089920 (logistic regression P=2.15 × 10(-120)) and 5 suggestive loci. The above 13 associated loci, harboured by candidates of ROBO1, GATA3, GBX2, FGF3, NRP2, EDNRB, SHROOM3, SEMA7A, PLCD3, KLF12 and EPAS1, are found to be enriched for genes involved in neural crest cell (NCC) development and vasculogenesis...
February 8, 2016: Nature Communications
N Godin-Heymann, S Brabetz, M M Murillo, M Saponaro, C R Santos, A Lobley, P East, P Chakravarty, N Matthews, G Kelly, S Jordan, E Castellano, J Downward
Suppression of detachment-induced cell death, known as anoikis, is an essential step for cancer metastasis to occur. We report here that expression of KLF12, a member of the Kruppel-like family of transcription factors, is downregulated in lung cancer cell lines that have been selected to grow in the absence of cell adhesion. Knockdown of KLF12 in parental cells results in decreased apoptosis following cell detachment from matrix. KLF12 regulates anoikis by promoting the cell cycle transition through S phase and therefore cell proliferation...
June 23, 2016: Oncogene
Hui Zhang, Xudong Zhu, Jing Chen, Yue Jiang, Qun Zhang, Chengcai Kong, Jun Xing, Lijun Ding, Zhenyu Diao, Xin Zhen, Haixiang Sun, Guijun Yan
BACKGROUND: Decidualization is a prerequisite for successful implantation and the establishment of pregnancy. Krüppel-like factor 12 (KLF12) is a negative regulator of endometrial decidualization in vitro. We investigated whether KLF12 was associated with impaired decidualization under conditions of repeated implantation failure (RIF). METHODS: Uterine tissues were collected from a mouse model of early pregnancy and artificial decidualization for immunohistochemistry, Western blot and real-time PCR analysis...
2015: Reproductive Biology and Endocrinology: RB&E
Sabine Hünten, Markus Kaller, Friedel Drepper, Silke Oeljeklaus, Thomas Bonfert, Florian Erhard, Anne Dueck, Norbert Eichner, Caroline C Friedel, Gunter Meister, Ralf Zimmer, Bettina Warscheid, Heiko Hermeking
We determined the effect of p53 activation on de novo protein synthesis using quantitative proteomics (pulsed stable isotope labeling with amino acids in cell culture/pSILAC) in the colorectal cancer cell line SW480. This was combined with mRNA and noncoding RNA expression analyses by next generation sequencing (RNA-, miR-Seq). Furthermore, genome-wide DNA binding of p53 was analyzed by chromatin-immunoprecipitation (ChIP-Seq). Thereby, we identified differentially regulated proteins (542 up, 569 down), mRNAs (1258 up, 415 down), miRNAs (111 up, 95 down) and lncRNAs (270 up, 123 down)...
October 2015: Molecular & Cellular Proteomics: MCP
Qun Zhang, Hui Zhang, Yue Jiang, Bai Xue, Zhenyu Diao, Lijun Ding, Xin Zhen, Haixiang Sun, Guijun Yan, Yali Hu
BACKGROUND: The transformation of endometrium into decidua is essential for normal implantation of the blastocyst. However, the post-transcriptional regulation and the miRNAs involved in decidualization remain poorly understood. Here, we examined microRNA-181a (miR-181a) expression in decidualized human endometrial stromal cell (hESC). In addition, we investigated the functional effect of miR-181a on hESC decidualization in vitro. METHODS: Quantitative real-time PCR (qRT-PCR) was used to detect the profile of miR-181a in decidualized hESC...
2015: Reproductive Biology and Endocrinology: RB&E
Zheng Hu, Da Zhu, Wei Wang, Weiyang Li, Wenlong Jia, Xi Zeng, Wencheng Ding, Lan Yu, Xiaoli Wang, Liming Wang, Hui Shen, Changlin Zhang, Hongjie Liu, Xiao Liu, Yi Zhao, Xiaodong Fang, Shuaicheng Li, Wei Chen, Tang Tang, Aisi Fu, Zou Wang, Gang Chen, Qinglei Gao, Shuang Li, Ling Xi, Changyu Wang, Shujie Liao, Xiangyi Ma, Peng Wu, Kezhen Li, Shixuan Wang, Jianfeng Zhou, Jun Wang, Xun Xu, Hui Wang, Ding Ma
Human papillomavirus (HPV) integration is a key genetic event in cervical carcinogenesis. By conducting whole-genome sequencing and high-throughput viral integration detection, we identified 3,667 HPV integration breakpoints in 26 cervical intraepithelial neoplasias, 104 cervical carcinomas and five cell lines. Beyond recalculating frequencies for the previously reported frequent integration sites POU5F1B (9.7%), FHIT (8.7%), KLF12 (7.8%), KLF5 (6.8%), LRP1B (5.8%) and LEPREL1 (4.9%), we discovered new hot spots HMGA2 (7...
February 2015: Nature Genetics
Hirofumi Nakaoka, Atsushi Tajima, Taku Yoneyama, Kazuyoshi Hosomichi, Hidetoshi Kasuya, Tohru Mizutani, Ituro Inoue
BACKGROUND AND PURPOSE: The rupture of intracranial aneurysm (IA) causes subarachnoid hemorrhage associated with high morbidity and mortality. We compared gene expression profiles in aneurysmal domes between unruptured IAs and ruptured IAs (RIAs) to elucidate biological mechanisms predisposing to the rupture of IA. METHODS: We determined gene expression levels of 8 RIAs, 5 unruptured IAs, and 10 superficial temporal arteries with the Agilent microarrays. To explore biological heterogeneity of IAs, we classified the samples into subgroups showing similar gene expression patterns, using clustering methods...
August 2014: Stroke; a Journal of Cerebral Circulation
George Pentheroudakis, Vassiliki Kotoula, Elena Fountzilas, George Kouvatseas, George Basdanis, Ioannis Xanthakis, Thomas Makatsoris, Elpida Charalambous, Demetris Papamichael, Epaminontas Samantas, Pavlos Papakostas, Dimitrios Bafaloukos, Evangelia Razis, Christos Christodoulou, Ioannis Varthalitis, Nicholas Pavlidis, George Fountzilas
BACKGROUND: Bevacizumab, an antibody neutralizing Vascular Endothelial Growth Factor (VEGF), is licensed for the management of patients with advanced colon cancer. However, tumor biomarkers identifying the molecular tumor subsets most amenable to angiogenesis modulation are lacking. METHODS: We profiled expession of 24526 genes by means of whole genome 24 K DASL (c-DNA-mediated, Annealing, Selection and Ligation) arrays, (Illumina, CA) in 16 bevacizumab-treated patients with advanced colon cancer (Test set)...
2014: BMC Cancer
Adam Frankel, Nicola Armour, Derek Nancarrow, Lutz Krause, Nicholas Hayward, Guy Lampe, B Mark Smithers, Andrew Barbour
The incidence of esophageal adenocarcinoma (EAC) has been increasing rapidly for the past 3 decades in Western (Caucasian) populations. Curative treatment is based around esophagectomy, which has a major impact on quality of life. For those suitable for treatment with curative intent, 5-year survival is ∼30%. More accurate prognostic tools are therefore needed, and copy number aberrations (CNAs) may offer the ability to act as prospective biomarkers in this regard. We performed a genome-wide examination of CNAs in 54 samples of EAC using single-nucleotide polymorphism (SNP) arrays...
April 2014: Genes, Chromosomes & Cancer
Xiaoyue Shen, Yali Hu, Yue Jiang, Hongyu Liu, Lihua Zhu, Xiaoyan Jin, Huizhi Shan, Xin Zhen, Lihua Sun, Guijun Yan, Haixiang Sun
Members of the KLFs family of transcription factors play roles in maternal endometrium development during embryo implantation. However, the specific role of KLF12 in endometrium development has not yet been described. In this study, we showed that KLF12 expression in human endometrial stromal cells (HESCs) was significantly decreased after decidualization stimulated by 8-Br-cAMP and medroxyprogesterone acetate (MPA). The adenovirus-mediated overexpression of KLF12 in HESCs significantly repressed the expression and secretion of decidualization biomarker genes and their products decidual prolactin (PRL) and insulin-like growth factor binding protein-1 (IGFBP-1) induced by 8-Br-cAMP and MPA...
March 29, 2013: Biochemical and Biophysical Research Communications
Gunaseelan Narayanan, Anuradha Poonepalli, Jinmiao Chen, Shvetha Sankaran, Srivats Hariharan, Yuan Hong Yu, Paul Robson, Henry Yang, Sohail Ahmed
Neurospheres are widely used to propagate and investigate neural stem cells (NSCs) and neural progenitors (NPs). However, the exact cell types present within neurospheres are still unknown. To identify cell types, we used single-cell mRNA profiling of 48 genes in 187 neurosphere cells. Using a clustering algorithm, we identified 3 discrete cell populations within neurospheres. One cell population [cluster unsorted (US) 1] expresses high Bmi1 and Hes5 and low Myc and Klf12. Cluster US2 shows intermediate expression of most of the genes analyzed...
December 10, 2012: Stem Cells and Development
Stefan Wieczorek, Julia U Holle, Stephanie Müller, Harald Fricke, Wolfgang L Gross, Jörg T Epplen
Wegener's granulomatosis (WG), characterized by systemic vasculitis and granulomatous inflammation, is a rare chronic rheumatic condition potentially sharing some etiopathological principles with other autoimmune disorders, e.g., rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Several large association studies have identified genetic risk factors for RA and SLE. Thereof, we have evaluated the relevance of the most promising ones in WG. 22 single nucleotide polymorphisms (SNPs) within or in the vicinity of CCL21, CD40, CDK6, IL21, IL2RB, IRF5, KIF5A, KLF12, MMEL1, PRKCQ, STAT4, TNFAIP3, and TRAF1/C5 have been genotyped in >600 German WG cases and >800 matched controls...
April 2010: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
Yu Nakamura, Toshiro Migita, Fumie Hosoda, Naoko Okada, Masahiro Gotoh, Yasuhito Arai, Michiyo Fukushima, Misao Ohki, Satoshi Miyata, Kengo Takeuchi, Issei Imoto, Hitoshi Katai, Toshiharu Yamaguchi, Johji Inazawa, Setsuo Hirohashi, Yuichi Ishikawa, Tatsuhiro Shibata
Gastric cancer is the second common malignant neoplasia in Japan, and its poorly differentiated form is a deadly disease. To identify novel candidate oncogenes contributing to its genesis, we examined copy-number alterations in 50 primary poorly differentiated gastric cancers using an array-based comparative genomic hybridization (array-CGH). Many genetic changes were identified, including a novel amplification of the 13q22 locus. Several genes are located in this locus, and selective knockdown of one for the Krüppel-like factor 12 (KLF12) induced significant growth-arrest in the HGC27 gastric cancer cell line...
October 15, 2009: International Journal of Cancer. Journal International du Cancer
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