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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...
August 19, 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...
May 23, 2016: 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
Maria Yamilet Noriega-Reyes, Miguel Angel Rivas-Torres, Luis Fernando Oñate-Ocaña, Albert Jordan Vallés, Noemi Baranda-Avila, Elizabeth Langley
Estrogen receptor alpha (ERα) has an established role in breast cancer biology. Transcriptional activation by ERα is a multistep process influenced by coactivator and corepressor proteins. This work shows that Pin2 interacting protein 1 (PINX1) interacts with the N-terminal domain of ERα and functions as a corepressor of ERα. Furthermore, it represses both AF-1 and AF-2 transcriptional activities. Chromatin immunoprecipitation assays verified that the interaction between ERα and PINX1 occurs on E2 regulated promoters and enhanced expression of PINX1 deregulates the expression of a number of genes that have a role in cell growth and proliferation in breast cancer...
October 15, 2015: Molecular and Cellular Endocrinology
Hai-Long Li, Li Han, Hai-Rong Chen, Fei Meng, Qing-Hua Liu, Zhen-Qiang Pan, Jin Bai, Jun-Nian Zheng
PIN2/TRF1-interacting telomerase inhibitor 1 (PinX1) is a novel cloned gene which has been identified as a major haploinsufficient tumor suppressor essential for maintaining telomerase activity, the length of telomerase and chromosome stability. This study explored the clinical significance and biological function of PinX1 in human clear cell renal cell carcinoma (ccRCC). The clinical relevance of PinX1 in ccRCC was evaluated using tissue microarray and immunohistochemical staining in two independent human ccRCC cohorts...
August 28, 2015: Oncotarget
Meilin Shi, Menghan Cao, Jun Song, Qinghua Liu, Hailong Li, Fei Meng, Zhenqiang Pan, Jin Bai, Junnian Zheng
BACKGROUND: PinX1 (PIN2/TRF1-interacting telomerase inhibitor 1) was suggested to be correlated with tumor progression. This study was designed to evaluate the role of PinX1 in human breast cancer. METHODS: To evaluate the function of PinX1 in breast cancer, we used a tissue microarray (TMA) of 405 human breast cancer patients and immunohistochemistry to analyze the correlation between PinX1 expression and clinicopathologic variables and patient survival. We also detected the abilities of cell migration and invasion in breast cancer by performing cell migration and invasion assay, gelatin zymography and western blot analysis...
2015: Molecular Cancer
Changwei Li, Wei Chen, Fan Jiang, Jeannette Simino, Sathanur R Srinivasan, Gerald S Berenson, Hao Mei
OBJECTIVES: To examine the associations of five GWAS-identified genes with carotid intima-media thickness (IMT) in a biracial sample from the Bogalusa Heart Study, and evaluate their participation in gene-smoking interactions. METHODS: Far wall IMTs of common carotid arteries were measured using high-resolution B-mode ultrasound. Both the gene-smoking interactions and single-marker associations were evaluated by linear models of carotid IMT levels, while the gene-based analyses were assessed through the truncated product method...
May 15, 2015: Gene
Peng-Jin Mei, Yan-Su Chen, Ying Du, Jin Bai, Jun-Nian Zheng
PinX1 induces apoptosis and suppresses cell proliferation in some cancer cells, and the expression of PinX1 is frequently decreased in some cancer and negatively associated with metastasis and prognosis. However, the precise roles of PinX1 in gliomas have not been studied. In this study, we found that PinX1 obviously reduced the gliomas cell proliferation through regulating the expressions of cell cycle-relative molecules to arrest cell at G1 phase and down-regulating the expression of component telomerase reverse transcriptase (hTERT in human), which is the hardcore of telomerase...
March 2015: Medical Oncology
Li Baichuan, Songshen Cao, Yunlai Liu
Liver-related putative tumor suppressor (lpts) is a liver-related tumor suppressor candidate gene initially isolated by positional candidate cloning method. Three translation products of lpts gene are found, that are LPTS-L, LPTS-S and LPTS-M respectively. The gene highly expresses in normal tissues but lowly in cancer tissues. The LPTS proteins can suppress the activity of telomerase and trigger apoptosis for tumor cells in vivo and in vitro, despite that the detailed anti-cancer mechanism remains undefined...
2015: Recent Patents on Anti-cancer Drug Discovery
Fariba Badrzadeh, Abolfazl Akbarzadeh, Nosratollah Zarghami, Mohammad Rahmati Yamchi, Vahide Zeighamian, Fateme Sadate Tabatabae, Morteza Taheri, Hossein Samadi Kafil
BACKGROUND: Herbal compounds such as curcumin which decrease telomerase and gene expression have been considered as beneficial tools for lung cancer treatment. In this article, we compared the effects of pure curcumin and curcumin-loaded NIPAAm-MAA nanoparticles on telomerase and PinX1 gene expression in a lung cancer cell line. MATERIALS AND METHODS: A tetrazolium-based assay was used for determination of cytotoxic effects of curcumin on the Calu-6 lung cancer cell line and telomerase and pinX1 gene expression was measured with real-time PCR...
2014: Asian Pacific Journal of Cancer Prevention: APJCP
Xiao-Peng Tian, Dong Qian, Li-Ru He, He Huang, Shi-Juan Mai, Chang-Peng Li, Xiao-Xia Huang, Mu-Yan Cai, Yi-Ji Liao, Hsiang-fu Kung, Yi-Xin Zeng, Dan Xie
Paclitaxel is a main ingredient in the combination chemotherapy treatment of advanced human cervical squamous cell carcinomas. We investigated the roles and underlying molecular mechanisms of PinX1 in cervical squamous cell carcinomas (CSCC) cells response to paclitaxel and its clinical significances. The expression dynamics of PinX1 was first examined by immunohistochemistry in 122 advanced CSCC patients treated with cisplatin/paclitaxel chemotherapy. The expression of PinX1 was significantly associated with the effects of cisplatin/paclitaxel chemotherapy in advanced CSCCs (P<0...
October 10, 2014: Cancer Letters
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