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Jun-Yao Wang, Lan Xiao, Jian-Ying Wang
Maintenance of the gut epithelial integrity under stressful environments requires epithelial cells to rapidly elicit changes in gene expression patterns to regulate their survival, adapt to stress, and keep epithelial homeostasis. Disruption of the intestinal epithelial integrity occurs commonly in patients with various critical illnesses, leading to the translocation of luminal toxic substances and bacteria to the blood stream. Recently, noncoding RNAs (ncRNAs) have emerged as a novel class of master regulators of gene expression and are fundamentally involved in many aspects of gut mucosal regeneration, protection, and epithelial barrier function...
October 4, 2016: Wiley Interdisciplinary Reviews. RNA
Jae-Young Lee, Sunghyun Park, Kwang-Soo Kim, Jeong-Jae Ko, Soohong Lee, Keun Pil Kim, Kyung-Soon Park
Sprouty (Spry) genes encode inhibitors of the receptor tyrosine kinase signaling cascade, which plays important roles in stem cells. However, the role of Spry4 in the stemness of embryonic stem cells has not been fully elucidated. Here, we used mouse embryonic stem cells (mESCs) as a model system to investigate the role of Spry4 in the stem cells. Suppression of Spry4 expression results in the decreases of cell proliferation, EB formation and stemness marker expression, suggesting that Spry4 activity is associated with stemness of mESCs...
June 2016: Balsaeng'gwa Saengsig
Yang Cao, Yinglei Liu, Xiaoyan Lu, Ying Wang, Haifeng Qiao, Manhua Liu
The identification of cancer-associated long noncoding RNA (lncRNA) is critical for us to understand cancer pathogenesis and development. The aim of this study was to evaluate the expression profile of the lncRNA SPRY4-IT1 in cervical cancer and to identify its clinical significance in cancer progression. The expression levels of SPRY4-IT1 in cervical cancer tissues were measured by quantitative real-time PCR, and its correlation with overall survival of cervical cancer patients was analyzed statistically. Our results showed that the expression levels of SPRY4-IT1 were higher in cervical cancer tissues than in adjacent normal tissues...
September 2016: FEBS Open Bio
Dong Cao, Qiong Ding, Wubin Yu, Ming Gao, Yilian Wang
The clinical significance and biological functions of long noncoding RNA SPRY4 intronic transcript 1 (SPRY4-IT1) in colorectal cancer (CRC) remain largely unclear. Herein, we are the first to report that the SPRY4-IT1 was significantly upregulated in CRC tissues, serum, and cells. Higher SPRY4-IT1 expression was markedly associated with advanced Tumor Node Metastasis (TNM) stage in a cohort of 84 CRC patients. Multivariate analyses indicated that SPRY4-IT1 expression could be useful as an independent predictor for overall survival...
2016: OncoTargets and Therapy
Faruk Hadziselimovic, Katharina Gegenschatz-Schmid, Gilvydas Verkauskas, Maria J Docampo-Garcia, Philippe Demougin, Vytautas Bilius, Dalius Malcius, Darius Dasevicius, Michael B Stadtler
The whole genome RNA profiling of testicular biopsies by DNA strand-specific RNA sequencing was examined to determine a potential causative role of isolated congenital cryptorchidism in azoospermia and/or infertility in the context of our previously published GeneChip data. Cryptorchid patients, aged 7 months to 5 years and otherwise healthy, were enrolled in this prospective study. During surgery, testicular tissue biopsies were obtained for histological examination and RNA sequencing. Fifteen patients were selected based on the histological results and were divided into 2 groups...
2016: Sexual Development: Genetics, Molecular Biology, Evolution, Endocrinology, Embryology, and Pathology of Sex Determination and Differentiation
Y Zhou, D-L Wang, Q Pang
OBJECTIVE: Long non-coding RNAs (lncRNAs) are emerging as biomarkers and as important regulators of the biological processes and tumorigenesis in cancer. The purpose of this study is to investigate the clinical significance of lncRNA SPRY4-IT1 in glioma. PATIENTS AND METHODS: The expression level of SPRY4-IT1 was examined by the quantitative Real-time PCR (qRT-PCR) in glioma tissues and control tissues and its association with overall survival of patients was analyzed by statistical analysis...
July 2016: European Review for Medical and Pharmacological Sciences
J Xue-Liang, W Ming-Dong, Z Ya-Bi, W Wang-Yue
OBJECTIVES: The function of long noncoding RNA SPRY4-IT1 in human esophageal squamous cell carcinoma (ESCC) has been showed in the former studies. The purpose of this study was to further analyze the underlined mechanisms responsible for its role in ESCC cells. MATERIALS AND METHODS: Quantitative reverse transcriptase polymerase chain reaction was firstly used to measure the expression of SPRY4-IT1 in 50 ESCC patients of different clinical stages. Loss of function approach was then applied to confirm the biological function, especially cell viabilities in cultured ESCC cells, by cell counting kit-8 and clonogenic assay...
December 2015: Indian Journal of Cancer
Fei Shen, Wen-Song Cai, Zhe Feng, Ji-Wei Chen, Jian-Hua Feng, Qi-Cai Liu, Yong-Ping Fang, Kun-Ping Li, Huan-Qing Xiao, Jie Cao, Bo Xu
Colorectal cancer (CRC) remains one of the most common cancers worldwide. Increasing evidence indicates that SPRY4 intronic transcript 1 (SPRY4-IT1) regulate cell growth, differentiation, apoptosis, and cancer progression. However, the expression and function of SPRY4-IT1 in the progression of CRC remains largely unknown. Here, we reported that SPRY4-IT1 was upregulated in CRC. Increased SPRY4-IT1 expression in CRC was associated with larger tumor size and higher clinical stage. In vitro experiments revealed that SPRY4-IT1 knockdown significantly inhibited CRC cell proliferation by causing G1 arrest and promoting apoptosis, whereas SPRY4-IT1 overexpression promoted cell proliferation...
July 6, 2016: Oncotarget
Wei Jing, Shanshan Gao, Man Zhu, Ping Luo, Xuan Jing, Hongyan Chai, Jiancheng Tu
The manifestation of hepatocellular carcinoma (HCC) involves a multi-factor, multi-step and complex process. Due to the lack of early prediction indices, numerous patients are diagnosed in their late stage. Recently, research in the field of non-coding RNAs (ncRNAs) has changed the original idea that ncRNA genes are just ̔noise̓. Cumulative evidence shows that long non-coding RNAs (lncRNAs) among ncRNAs play an increasingly important role in epigenetics, pre-transcription and post-transcription. In the present study, we focused on the expression pattern of lncRNA SPRY4 intronic transcript 1 (SPRY4-IT1) and its clinical significance in HCC diagnostics...
August 2016: Oncology Reports
Teng Liu, Song-Ke Shen, Jian-Gui Xiong, Yuan Xu, Han-Qi Zhang, Hai-Jun Liu, Zheng-Gen Lu
Long noncoding RNA SPRY4-IT1 has been reported to promote melanoma cell growth and invasion, and to block apoptosis. The purpose of this study was to investigate the clinical significance of SPRY4-IT1 in patients with malignant melanoma. The relative expression levels of SPRY4-IT1 were measured in plasma samples from 70 patients and 79 healthy controls by quantitative reverse transcriptase polymerase chain reaction. SPRY4-IT1 expression is high in melanoma patients but low in healthy controls, and is closely associated with tumor site and tumor stage...
February 2016: FEBS Open Bio
Hidenori Kitai, Hiromichi Ebi, Shuta Tomida, Konstantinos V Floros, Hiroshi Kotani, Yuta Adachi, Satoshi Oizumi, Masaharu Nishimura, Anthony C Faber, Seiji Yano
UNLABELLED: KRAS is frequently mutated in lung cancer. Whereas MAPK is a well-known effector pathway of KRAS, blocking this pathway with clinically available MAPK inhibitors is relatively ineffective. Here, we report that epithelial-to-mesenchymal transition rewires the expression of receptor tyrosine kinases, leading to differential feedback activation of the MAPK pathway following MEK inhibition. In epithelial-like KRAS-mutant lung cancers, this feedback was attributed to ERBB3-mediated activation of MEK and AKT...
July 2016: Cancer Discovery
Neng Ru, Jie Liang, Fan Zhang, Weifei Wu, Feifan Wang, Xinzong Liu, Yuanli Du
Osteosarcoma is an aggressive tumor and the most common malignancy of the skeleton. Due to pulmonary metastasis, the 5-year survival rate is still unsatisfactory. It has been reported that SPRY4 intronic transcript 1 (SPRY4-IT1) promotes cell growth, invasion, and inhibits apoptosis in several cancers. However, the role of SPRY4-IT1 in osteosarcoma remains unclear. In the present study, we investigated the role of SPRY4-IT1 in osteosarcoma cells. Loss- and gain-of-function assays demonstrated that SPRY4-IT1 promoted cell proliferation, migration, and invasion in osteosarcoma...
June 2016: DNA and Cell Biology
Hongyu Jing, Lucy Liaw, Robert Friesel, Calvin Vary, Shucheng Hua, Xuehui Yang
BACKGROUND: Cancer stem cells contribute to tumor initiation, heterogeneity, and recurrence, and are critical targets in cancer therapy. Sprouty4 (Spry4) is a potent inhibitor of signal transduction pathways elicited by receptor tyrosine kinases, and has roles in regulating cell proliferation, migration and differentiation. Spry4 has been implicated as a tumor suppressor and in modulating embryonic stem cells. OBJECTIVES: The purpose of this research was to test the novel idea that Spry4 regulates cancer stem cell properties in breast cancer...
2016: Cancer Cell International
Fei Cui, Duoguang Wu, Xiaotian He, Wenjian Wang, Jingle Xi, Minghui Wang
The biology of esophageal squamous cell carcinoma (ESCC) remains poorly understood. Long noncoding RNAs (lncRNAs) are found to be dysregulated in a variety of cancers, including ESCC. SPRY4-IT1 has been recently revealed as oncogenic regulator or tumor suppressors in different cancers; however, whether SPRY4-IT1 is involved in ESCC remains poorly understood. To investigate the role of SPRY4-IT1 in ESCC, we evaluated the SPRY4-IT1 expression levels in a series of ESCC patients and a panel of ESCC cell line using qRT-PCR...
August 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Y Xu, M Qiu, Y Chen, J Wang, W Xia, Q Mao, L Yang, M Li, F Jiang, L Xu, R Yin
Esophageal squamous cell carcinoma (ESCC) is one of the major causes of cancer death worldwide, especially in Eastern Asia. Due to the poor prognosis, it is necessary to further dissect the underlying mechanisms and explore therapeutic targets of ESCC. Recently, studies show that long noncoding RNAs (lncRNAs) have critical roles in diverse biological processes, including tumorigenesis. Increasing evidence indicates that some lncRNAs are widely involved in the development and progression of ESCC, such as HOTAIR, SPRY4-IT1 and POU3F3...
February 2, 2016: Diseases of the Esophagus: Official Journal of the International Society for Diseases of the Esophagus
Wei Zhao, Joseph Mazar, Bongyong Lee, Junko Sawada, Jian-Liang Li, John Shelley, Subramaniam Govindarajan, Dwight Towler, John S Mattick, Masanobu Komatsu, Marcel E Dinger, Ranjan J Perera
The long noncoding RNA SPRIGHTLY (formerly SPRY4-IT1), which lies within the intronic region of the SPRY4 gene, is up-regulated in human melanoma cells compared to melanocytes. SPRIGHTLY regulates a number of cancer hallmarks, including proliferation, motility, and apoptosis. To better understand its oncogenic role, SPRIGHTLY was stably transfected into human melanocytes, which resulted in increased cellular proliferation, colony formation, invasion, and development of a multinucleated dendritic-like phenotype...
April 2016: Journal of Investigative Dermatology
Wai-Kin So, Jung-Chien Cheng, Yingtao Liu, Congjian Xu, Jianfang Zhao, Vincent T W Chang, Peter C K Leung
Sprouty (SPRY) proteins are well-characterized factors that inhibit receptor tyrosine kinase (RTK)-mediated activation of cellular signaling pathways. The down-regulation of SPRY4 expression has been reported in human ovarian cancer. However, the specific roles and mechanisms by which SPRY4 affects ovarian cancer progression are completely unknown. Amphiregulin (AREG) binds exclusively to the epidermal growth factor receptor (EGFR) and has been considered to be a dominant autocrine/paracrine EGFR ligand in ovarian cancer...
July 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Lan Xiao, Jaladanki N Rao, Shan Cao, Lan Liu, Hee Kyoung Chung, Yun Zhang, Jennifer Zhang, Yulan Liu, Myriam Gorospe, Jian-Ying Wang
Epithelial cells line the intestinal mucosa and form an important barrier to a wide array of noxious substances in the lumen. Disruption of the barrier integrity occurs commonly in various pathologies. Long noncoding RNAs (lncRNAs) control diverse biological processes, but little is known about the role of lncRNAs in regulation of the gut permeability. Here we show that the lncRNA SPRY4-IT1 regulates the intestinal epithelial barrier function by altering expression of tight junction (TJ) proteins. SPRY4-IT1 silencing led to dysfunction of the epithelial barrier in cultured cells by decreasing the stability of mRNAs encoding TJ proteins claudin-1, claudin-3, occludin, and JAM-1 and repressing their translation...
February 15, 2016: Molecular Biology of the Cell
Lars Klimaschewski, Belen Pinar Sueiro, Luis Martinez Millan
Down-regulation of Sprouty proteins promotes axon regeneration in lesioned nerves and prevents neurodegeneration following excitotoxic brain injury. In this study, siRNAs directed against Sprouty2 and -4 were stereotactically injected along with the vasoconstrictive peptide endothelin-1 to create cortical infarcts in the adult rat brain. A single injection of Sprouty2/4 siRNAs (25μM each) significantly decreased Spry2 and Spry4 mRNA levels two days later and diminished the size of the injury area in the subchronic phase following vasoconstriction...
January 26, 2016: Neuroscience Letters
Sitthisak Thongrong, Barbara Hausott, Letizia Marvaldi, Alexandra S Agostinho, Luca Zangrandi, Johannes Burtscher, Barbara Fogli, Christoph Schwarzer, Lars Klimaschewski
Sprouty (Spry) proteins play a key role as negative feedback inhibitors of the Ras/Raf/MAPK/ERK pathway downstream of various receptor tyrosine kinases. Among the four Sprouty isoforms, Spry2 and Spry4 are expressed in the hippocampus. In this study, possible effects of Spry2 and Spry4 hypomorphism on neurodegeneration and seizure thresholds in a mouse model of epileptogenesis was analyzed. The Spry2/4 hypomorphs exhibited stronger ERK activation which was limited to the CA3 pyramidal cell layer and to the hilar region...
May 2016: Hippocampus
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