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Shengguang Wang, Hua Zhang, Jianquan Zhu, Chenguang Li, Jinfang Zhu, Bowen Shi, Bin Zhang, Changli Wang
PinX1 has been identified as a suppressor of telomerase enzymatic activity. However, the tumour-suppressive roles of PinX1 in different types of human cancers are unclear. PinX1 expression status and its correlation with clinicopathological features in non-small-cell lung cancer (NSCLC) have not been investigated. Accordingly, in this study, we aimed to evaluate the roles of PinX1 in NSCLC. PinX1 expression status was examined by immunohistochemistry using tissue microarray from a total of 158 patients. Correlations among PinX1 expression, clinicopathological variables, and patient survival were analysed...
2017: BioMed Research International
Haiying Zhao, Yunfeng Cao, Guoqiang Wang, Zengxiang Luo
We investigated the expression of FOXC2, PinX1, Ki-67 and Cyclin D1 in cutaneous cell carcinoma. We collected 30 cutaneous squamous cell carcinoma (SCC), 30 cutaneous basal cell carcinoma (BCC) and 30 normal skin tissues. The protein expression and gene expression of FOXC2, endogenous telomerase-inhibiting gene PinX1, Ki-67 and Cyclin D1 was measured by immunohistochemistry (IHC) and semi-quantitative reverse transcription polymerase chain reaction (RT-PCR), respectively. In SCC and BCC tissues, the positive rate of protein expression and mRNA level of PinX1 were both significantly lower than those in normal tissues...
July 2017: Oncology Letters
Wei-Juan Huang, Mei Li, Xiao-Han Jin, Xiao-Jia Huang, Wei Zhao, Xiao-Peng Tian
Pin2/TRF1-interacting telomere inhibitor 1 (PinX1) was originally identified as a telomerase inhibitor, involved in maintaining telomerase activity, telomere length, and chromosomal stability. However, research has shown that PinX1 can have opposing molecular status in its expression patterns in several other tumor types. We thus investigated the genetic profile and biological implication of PinX1 in several human cancers using the cBioportal database. Our results showed that PinX1 deletion accounted for the most alterations, with the frequency of its deletion regularly occurring in pathological types of carcinosarcoma and adenocarcinoma...
June 21, 2017: Oncotarget
Yu-Zhen Feng, Qing-Yan Zhang, Mei-Ting Fu, Zhen-Fei Zhang, Min Wei, Jue-Yu Zhou, Rong Shi
Human Pinx1 protein, associated with shelterin proteins, is widely revealed as a haploinsufficient tumor suppressor. Growing evidence has manifested the deregulation of PinX1 in distinct cancers. Nonetheless, the loss status of PinX1 and its diagnostic, prognostic and clinicopathological significance in Basal-like breast cancer are still unclear. In the present study, the PinX1 expression levels of breast cancer tissues were investigated by qRT-PCR and immunoblotting assays. Then immunohistochemistry (IHC) was performed to detect PinX1 expression on a tissue microarray...
July 2017: Oncology Reports
Xiao-Peng Tian, Xiao-Han Jin, Mei Li, Wei-Juan Huang, Dan Xie, Jia-Xing Zhang
BACKGROUND: The telomerase/telomere interacting protein PinX1 has been suggested as a tumor suppressor. However, the clinical and biological significance of PinX1 in human non-small cell lung cancer (NSCLC) is unclear. METHODS: PinX1 gene/expression pattern and its association with NSCLC patient survival were analyzed in cBioportal Web resource and two cohorts of NSCLC samples. A series of in vivo and in vitro assays were performed to elucidate the function of PinX1 on NSCLC cells proliferation and underlying mechanisms...
April 4, 2017: Molecular Cancer
Derek Hang-Cheong Cheung, Sai-Tim Ho, Kwok-Fai Lau, Rui Jin, Ya-Nan Wang, Hsiang-Fu Kung, Jun-Jian Huang, Pang-Chui Shaw
Telomerase activation and telomere maintenance are critical for cellular immortalization and transformation. PIN2/TERF1-interacting telomerase inhibitor 1 (PinX1) is a telomerase regulator and the aberrant expression of PinX1 causes telomere shortening. Identifying PinX1-interacting proteins is important for understanding telomere maintenance. We found that PinX1 directly interacts with nucleophosmin (NPM), a protein that has been shown to positively correlate with telomerase activity. We further showed that PinX1 acts as a linker in the association between NPM and hTERT, the catalytic subunit of telomerase...
March 3, 2017: Scientific Reports
Raquel López-Mejías, Alfonso Corrales, Esther Vicente, Montserrat Robustillo-Villarino, Carlos González-Juanatey, Javier Llorca, Fernanda Genre, Sara Remuzgo-Martínez, Trinidad Dierssen-Sotos, José A Miranda-Filloy, Marco A Ramírez Huaranga, Trinitario Pina, Ricardo Blanco, Juan J Alegre-Sancho, Enrique Raya, Verónica Mijares, Begoña Ubilla, Iván Ferraz-Amaro, Carmen Gómez-Vaquero, Alejandro Balsa, Francisco J López-Longo, Patricia Carreira, Isidoro González-Álvaro, J Gonzalo Ocejo-Vinyals, Luis Rodríguez-Rodríguez, Benjamín Fernández-Gutiérrez, Santos Castañeda, Javier Martín, Miguel A González-Gay
A genetic component influences the development of atherosclerosis in the general population and also in rheumatoid arthritis (RA). However, genetic polymorphisms associated with atherosclerosis in the general population are not always involved in the development of cardiovascular disease (CVD) in RA. Accordingly, a study in North-American RA patients did not show the association reported in the general population of coronary artery disease with a series of relevant polymorphisms (TCF21, LPA, HHIPL1, RASD1-PEMT, MRPS6, CYP17A1-CNNM2-NT5C2, SMG6-SRR, PHACTR1, WDR12 and COL4A1-COL4A2)...
January 6, 2017: Scientific Reports
Jing Li, Yunfang Yao, Yu Chen, Xiao Xu, Yongquan Lin, Zhilong Yang, Wentao Qiao, Juan Tan
Enterovirus 71 (EV71) is an emerging pathogen causing hand, foot, and mouth disease (HFMD) and fatal neurological diseases in infants and young children due to their underdeveloped immunocompetence. EV71 infection can induce cellular apoptosis through a variety of pathways, which promotes EV71 release. The viral protease 3C plays an important role in EV71-induced apoptosis. However, the molecular mechanism responsible for 3C-triggered apoptosis remains elusive. Here, we found that EV71 3C directly interacted with PinX1, a telomere binding protein...
January 15, 2017: Journal of Virology
Xiang-Kui Fan, Rui-Hua Yan, Xiang-Qun Geng, Jing-Shan Li, Xiang-Ming Chen, Jian-Zhe Li
In the present study, to investigate the expression of PinX1 gene and its functional effects in human esophageal carcinoma (Eca)-109 cell line, expression vectors of human PinX1 (pEGFP-C3-PinX1) and its small interfering RNA (PinX1-FAM-siRNA) were constructed and transfected into Eca-109 cells using Lipofectamine 2000. Firstly, the mRNA expression level of PinX1 was examined using reverse transcription-polymerase chain reaction (RT-PCR). Once successful transfection was achieved, the effects on the mRNA level of human telomerase reverse transcriptase (hTERT), telomerase activity, cell proliferation and apoptosis were examined by semi-quantitative RT-PCR, stretch PCR, MTT assay and flow cytometry, respectively...
October 2016: Experimental and Therapeutic Medicine
Hai-Long Li, Jun Song, Hong-Mei Yong, Ping-Fu Hou, Yan-Su Chen, Wen-Bo Song, Jin Bai, Jun-Nian Zheng
PIN2/TRF1-interacting telomerase inhibitor 1 (PinX1) is a novel cloned gene located at human chromosome 8p23, playing a vital role in maintaining telomeres length and chromosome stability. It has been demonstrated to be involved in tumor genesis and progression in most malignancies. However, some researches showed opposing molecular status of PinX1 gene and its expression patterns in several other types of tumors. The pathogenic mechanism of PinX1 expression in human malignancy is not yet clear. Moreover, emerging evidence suggest that PinX1 (especially its TID domain) might be a potential new target cancer treatment...
October 4, 2016: Oncotarget
Dong Qian, Jingjing Cheng, Xiaofeng Ding, Xiuli Chen, Xi Chen, Yong Guan, Bin Zhang, Jiefu Wang, Puchun Er, Minghan Qiu, Xianliang Zeng, Yihang Guo, Huanhuan Wang, Lujun Zhao, Dan Xie, Zhiyong Yuan, Ping Wang, Qingsong Pang
PinX1 plays positive and negative roles in the maintenance of telomerase and telomeres, as well as in tumorigenesis. The aim of the present study was to investigate the expression and clinical significance of PinX1 in colorectal carcinoma (CRC) and to determine the effect of PinX1 on CRC cell proliferation and apoptosis. A total of 86 CRC patients treated with radical resection and 5-fluorouracil-based adjuvant chemotherapy were enrolled in this study. The expression dynamics of PinX1 was detected by immunohistochemistry in the CRC patients and 25 normal colonic mucosa controls...
2016: OncoTargets and Therapy
Methee Sriprapun, Natthaya Chuaypen, Apichaya Khlaiphuengsin, Nutcha Pinjaroen, Sunchai Payungporn, Pisit Tangkijvanich
Hepatocellular carcinoma (HCC) is major health problem with high mortality rates, especially in patients with hepatitis B virus (HBV) infection. Telomerase function is one of common mechanisms affecting genome stability and cancer development. Recent studies demonstrated that genetic polymorphisms of telomerase associated genes such as telomerase associated protein 1 (TEP1) rs1713449 and PIN2/TERF1-interacting telomerase inhibitor 1 (PINX1) rs1469557 may be associated with risk of HCC and other cancers. In this study, 325 patients with HCC and 539 non-HCC groups [193 healthy controls, 80 patients with HBV-related liver cirrhosis (LC) and 266 patients with HBV-related chronic hepatitis (CH)] were enrolled to explore genetic polymorphisms of both SNPs using the allelic discrimination method based on MGB probe TaqMan real time PCR...
2016: Asian Pacific Journal of Cancer Prevention: APJCP
J Yu, Q Liang, J Wang, K Wang, J Gao, J Zhang, Y Zeng, P W Y Chiu, E K W Ng, J J Y Sung
REC8 meiotic recombination protein (REC8) was found to be preferentially methylated in gastric cancer (GC) using promoter methylation array. We aimed to elucidate the epigenetic alteration and biological function of REC8 in GC. REC8 was downregulated in 100% (3/3) of Epstein-Barr virus (EBV)-positive and 80% (8/10) of EBV-negative GC cell lines by promoter methylation, but the expression could be restored through demethylation treatment. Protein expression of REC8 was significantly lower in human primary gastric tumors than in adjacent non-tumor tissues...
January 12, 2017: Oncogene
Marie H Geisel, Stefan Coassin, Nicole Heßler, Marcus Bauer, Lewin Eisele, Raimund Erbel, Margot Haun, Frauke Hennig, Susanna Moskau-Hartmann, Barbara Hoffmann, Karl-Heinz Jöckel, Lyudmyla Kedenko, Stefan Kiechl, Barbara Kollerits, Amir-Abbas Mahabadi, Susanne Moebus, Gudrun Nürnberg, Peter Nürnberg, Bernhard Paulweber, Maren Vens, Johann Willeit, Karin Willeit, Thomas Klockgether, Andreas Ziegler, André Scherag, Florian Kronenberg
Carotid intima media thickness (cIMT) is a marker for subclinical atherosclerosis. The most recent genome-wide association meta-analysis (GWAMA) from the CHARGE consortium identified four genomic regions showing either significant (ZHX2, APOC1, PINX1) or suggestive evidence (SLC17A4) for an association. Here we assess these four cIMT loci in a pooled analysis of four independent studies including 5446 individuals by providing updated unbiased effect estimates of the cIMT association signals. The pooled estimates of our four independent samples pointed in the same direction and were similar to those of the GWAMA...
June 2016: Atherosclerosis
Jia-Hui Xu, Shi-Lian Hu, Guo-Dong Shen, Gan Shen
OBJECTIVES: Paclitaxel (PTX) is frequently used in the clinical treatment of solid tumors. But the PTX-resistance is a great obstacle in cancer treatment. Exploration of the mechanisms of drug resistance suggests that tumor suppressor genes (TSGs) play a key role in the response of chemotherapeutic drugs. TSGs, a set of genes that are often inactivated in cancers, can regulate various biological processes. In this study, an overview of the contribution of TSGs to PTX resistance and their underlying relationship in cancers are reported by using GeneMANIA, a web-based tool for gene/protein function prediction...
2016: Cancer Cell International
Congxiang Shen, Yanhui Liu, Zhong Wen, Keke Yang, Guanxue Li, Shenhua Zhang, Xinyu Zhang
OBJECTIVE: To explore the influence and mechanism of PinX1 gene on the chemotherapy sensitivity of nasopharyngeal carcinoma cells in response to Cisplatin. METHODS: Transfected nasopharyngeal carcinoma 5-8F cell lines with pCDH-CMV-PinX1-copGFP vector constructed by lentivirus to generate Lenti-PinX1-5-8F cells containing PinX1 gene, using Lenti-Ctrl-5-8F cell (blank vector without PinX1 gene was used to transfect 5-8F cell lines) and 5-8F cell as controls. Expression of PinX1 gene, telomerase activity, the inhibition of cancer cells proliferation, combined anticancer effect with Cisplatin and the expression of lung resistance protein (LRP) and Bcl-2 were detected with fluorescent quantitation polymerase chain reaction (PCR), flow cytometry, thiazolyl blue (MTT) method, areole test, Western blot and drug sensitivity test, respectively, in four groups (Lenti-PinX1-5-8F cell + Cisplatin, Lenti-PinX1-5-8F cell, Cisplatin and 5-8F cell) so as to explore the influence and mechanism of PinX1 gene on the chemotherapy sensitivity of nasopharyngeal carcinoma cells in response to Cisplatin...
June 23, 2015: Zhonghua Yi Xue za Zhi [Chinese medical journal]
J P Li, S W Zhu, Y H Chen, X L Wang, X Gao
Telomeres have emerged as a promising and important factor modulating cellular and organism responses to ionizing radiation (IR). Pin2/TRF1 interacting protein X1 (PinX1) is an intrinsic telomerase inhibitor and a putative tumor suppressor gene in human cancers. The aim of this study is to investigate the role PinX1 in osteosarcoma (OS) radioresistance. A telomerase-positive OS cell line Saos-2 and a telomerase-negative OS cell line U2OS were used. PinX1 shRNA lentiviral vetors were constructed and transfected to cells...
2015: Neoplasma
Jin Bai, Yan-Su Chen, Peng-Jin Mei, Qing-Hua Liu, Ying Du, Jun-Nian Zheng
PinX1, a conserved nuclear protein, could maintain telomere integrity and plays an important role in regulating telomerase activity. It has been reported that the expression of PinX1 is down-regulated in some cancer and associated with cancer prognosis. However, the value of PinX1 in gliomas has not been studied. In this study, two independent retrospective gliomas cohorts with the corresponding gliomas tissue microarrays (TMAs) were established to detect the expression level of PinX1 and the correlation of PinX1 expression with the clinicopathological features and the patients' survival...
2015: International Journal of Clinical and Experimental Pathology
Wenying Deng, Nanlin Jiao, Ning Li, Xiangbin Wan, Suxia Luo, Youwei Zhang
Previous studies suggest that Pin2/TRF1 interacting protein X1 (PinX1) is an intrinsic telomerase inhibitor and a putative tumor suppressor gene in human cancers. The aims of this study were to investigate PinX1 expression status in colorectal cancer (CRC) specimens and to clarify its clinical significance. A total of 83 CRC patients treated with radical resection and 5-fluorouracil (5-FU) based adjuvant chemotherapy were enrolled in this study. Immunohistochemistry was used to detect PinX1 and human telomerase reverse transcriptase (hTERT) protein expression in paired tumor and adjacent normal tissues...
July 2015: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Ponnarath Keo, Joong Sub Choi, Jaeman Bae, Yhong-Hee Shim, Bong-Kyeong Oh
PinX1, a nucleolar protein of 328 amino acids, inhibits telomerase activity, which leads to the shortening of telomeres. The C-terminal region of PinX1 is responsible for its nucleolar localization and binding with TERT, a catalytic component of telomerase. A fraction of TERT localizes to the nucleolus, but the role of TERT in the nucleolus is largely unknown. Here, we report a functional connection between PinX1 and TERT regarding PinX1 stability. The C-terminal of PinX1(205-328), a nucleolar fragment, was much more stable than the N-terminal of PinX1(1-204), a nuclear fragment...
September 2015: Molecules and Cells
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