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Expression of Survivin and Its splice variants in Gastric Cancer

Journal of Huazhong University of Science and Technology(Medical Sciences) 2007年第4期27卷 393-398页

作者：程正江胡丽华付文荣张勤廖晓峰 Department of Clinical Laboratory Medicine Union HospitalTongji Medical CollegeHuazhong University of Science and Technology Department of Pathology Xiangfan HospitalTongji Medical CollegeHuazhong University of Science and Technology Department of General Surgery Xiangfan HospitalTongji Medical CollegeHuazhong University of Science and Technology

Survivin variants specific real time quantitative RT-PCR was developed to analyze their expression in 53 paired cancer and para-cancerous tissues, and the expression of the wild-type survivin protein was detected by immunohistochemistry. The results showed that survivin mRNA and protein were expressed in gastric cancer and para-cancerous tissues, The survivin-2B was dominantly expressed in para-cancerous tissues, whereas the survivin-△Ex3 was more frequently detected in cancer tissues. The positive rate of survivin-2a was 100% in both cancer and para-cancerous tissues, but its relative transcript expression level was not significantly increased in cancer tissues in comparison with para-cancerous tissues. The correlation analysis revealed that the expression of survivin-2a mRNA was significantly associated with that of total survivin （rs=0.4178, P=0.0018）, whereas inversely to that of survivin-△EX3 （rs=-0.4506, P=0.0007）. It was suggested that survivin-2a may act as an antagonist of survivin-△EX3. The balance between antiapoptotic survivin iso-forms and nonantiapoptotic ones may play an important role in tumorigenesis and tumor progression, Promising value is hinted to analyze survivin and its variants in tumor early diagnosis and distinguishing malignant tumors from benign ones.

关键词： survivin splice variants real-time PCR

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UHRF1/DNMT1—MZF1 axis-modulated intragenic site-specific CpGI methylation confers divergent expression and opposing functions of PRSS3 isoforms in lung cancer

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Acta Pharmaceutica Sinica B 2023年第5期13卷 2086-2106页

作者： Shuye Lin Hanli Xu Lin Qin Mengdi Pang Ziyu Wang Meng Gu Lishu Zhang Cong Zhao Xuefeng Hao Zhiyun Zhang Weimin Ding Jianke Ren Jiaqiang Huang Cancer Research Center Beijing Chest HospitalCapital Medical UniversityBeijing Tuberculosis and Thoracic Tumor InstituteBeijing 101149China College of Life Sciences&Bioengineering Beijing Jiaotong UniversityBeijing 100044China Department of Endoscopic Diagnosis and Treatment Beijing Chest HospitalCapital Medical UniversityBeijing Tuberculosis and Thoracic Tumor InstituteBeijing 101149China CAS Key Laboratory of Computational Biology Shanghai Institute of Nutrition and HealthUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200031China

As confusion mounts over RNA isoforms involved in phenotypic plasticity,aberrant CpG methylation-mediated disruption of alternative splicing is increasingly recognized as a driver of intratumor heterogeneity(ITH).Protease serine 3(PRSS3),possessing four splice variants(PRSS3-SVs;PRSS3-V1—V4),is an indispensable trypsin that shows paradoxical effects on cancer ***,we found that PRSS3 transcripts and their isoforms were divergently expressed in lung cancer,exhibiting opposing functions and clinical outcomes,namely,oncogenic PRSS3-V1 and PRSS3-V2 versus tumorsuppressive PRSS3-V3,by targeting different downstream *** identified an intragenic CpG island(iCpGI)in *** of iCpGI was mediated by UHRF1/DNMT1 complex interference with the binding of myeloid zinc finger 1(MZF1)to regulate PRSS3 *** garlic-derived compound diallyl trisulfide cooperated with 5-aza-2'-deoxycytidine to exert antitumor effects in lung adenocarcinoma cells through site-specific iCpGI demethylation specifically allowing MZF1 to upregulate PRSS3-V3 *** silencing of PRSS3-V3 via i CpGI methylation(iCpGIm)in BALF and tumor tissues was associated with early clinical progression in patients with lung cancer but not in those with squamous cell carcinoma or inflammatory ***,UHRF1/DNMT1—MZF1 axismodulated site-specific iCpGIm regulates divergent expression of PRSS3-SVs,conferring nongenetic functional ITH,with implications for early detection of lung cancer and targeted therapies.

关键词： Lung cancer Intratumor heterogeneity splice variants Intragenic CpG methylation Protease serine 3 Myeloid zinc finger 1 UHRF1/DNMT1 5-Aza-CdR

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Molecular characterization of thyroid peroxidase gene in porcine (sus scrofa)

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Journal of Genetics and Genomics 2010年第6期37卷 381-388页

作者： Ying Wang Xiaofeng Zhao Xiaoling Jiang Xuchuan Hua Ningying Xu College of Animal Sciences Zhejiang University Hangzhou 310029 China

Thyroid peroxidase （TPO） is the key enzyme involved in thyroid hormone synthesis. Several mutations in the TPO gene may affect the normal growth and development of mammals. In this study, the TPO gene was mapped, its expression level was determined in thyroid grand at the age of 1, 20, 45, 60, 90, 120 and 150 days for Jinhua pig, the alternative splicing form was searched and the single nucleotide polymorphism （SNP, A/G642） of TPO gene was analyzed. The results showed that the porcine TPO was mapped to 3q22-27, the expres- sion level of TPO was relatively stable among the various ages and two novel transcript variants in porcine TPO gene were found： the splicing variant TPO-2 lacked exon 8, while TPO-3 lacked exon 8 and exon 14, 15, 16. Moreover, we found that the SNP of A/G642in the fourteenth exon of TPO gene was significantly associated with ham weight （P 〈 0.05）. Our results provided important basis on the regulation and metabolism of the thyroid gland in animals.

关键词： thyroid peroxidase (TPO) porcine (sus scrofa) chromosome mapping SNP splice variants

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Androgen receptor variant-7： an important predictive biomarker in castrate resistant prostate cancer

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Asian Journal of Andrology 2015年第3期17卷 439-440页

作者： Oliver Sartor Yan Dong Department of Medicine and Urology Tulane Cancer Center Tulane University School of Medicine New Orleans LA USA Department of Structural and Cellular Biology Tulane Cancer Center Tulane University School of Medicine New Orleans LA USA National Engineering Laboratory for AIDS Vaccine College of Life Sciences Jilin University Changchun Jilin. China

The recent manuscript in New England Journal of Medicine by Antonarakis et al. has important clinical implications. This study evaluates mRNA expression of a particular androgen receptor splice variant-7 （AR-V7）, in circulating tumor cells （CTCs） from metastatic castrate-resistant prostate cancer （mCRPC） patients receiving enzalutamide or abiraterone. The findings were striking, none of the 18 patients with detectable AR-V7 in CTCs had prostate-specific antigen （PSA） responses.

关键词： ENZALUTAMIDE MDV3100 ABIRATERONE ACETATE ANTITUMOR-ACTIVITY splice variants DOCETAXEL THERAPY

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Role of β-microseminoprotein from prostate cancer initiationto recurrence: A mini-review

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World Journal of Clinical Urology 2014年第1期3卷 20-30页

作者： Nishi Karunasinghe Karen Bishop Pamela Murray Yuanye Xu Megan Goudie Lance Ng Shuotun Zhu Dug Yeo Han Lynnette R Ferguson Jonathan Masters Benji Benjamin Michael Holmes Auckland Cancer Society Research Centre Faculty of Medical and Health Sciences The University of Auckland Discipline of Nutrition Faculty of Medical and Health Sciences The University of Auckland Urology Department Auckland Hospital Radiology Department Auckland Hospital Urology Department Waikato Hospital

Medline/Pubmed articles relevant to this topic were considered using the search terms ?-microseminoprotein, MSMB, prostate secretory protein of 94 amino acids and PSP94. Full articles were retrieved when the abstract was considered relevant. In addition, other data related to this topic including our own are discussed. Summary of fi ndings-?-microseminoprotein(MSMB) is increasingly being considered as a marker for prostatecancer, as reduced levels have been associated with the disease. Here we review various aspects of this protein including its biological and physiological variants, binding proteins and immune modulation; its importance as a marker for biochemical recurrence of prostate cancer; prostate cancer related splice variants and its therapeutic utility. Two of the most important properties of MSMB are related to anticancer functions and immune modulation. Predominant expression of two(short and full-length) splice variants of MSMB has been observed from normal prostate and several other tissues. In benign prostate hyperplasia the short isoform is dominant, constituting 98% of this isoform, whereas in prostate cancer 96% constitute the fulllength isoform. The MSMB promoter single nucleotide polymorphism rs10993994 with the C allele functions as an activated cyclic adenosine monophosphate response element binding protein binding site. This C variant of rs10993994 could be responsible for the production of splice variants under variable conditions. MSMB has binding motifs to a few known proteins including immunoglobulin G and several Cysteine-rich secretory proteins family proteins. MSMB bound to these proteins is considered as immune modulating. Use of MSMB as a urinary marker for detecting aggressive prostate cancers that could resist radiation and surgical treatments, seems possible, but needs further investigation. The ratio of MSMB splice variants could also be a possible approach in understanding prostate cancers, with higher ratios indicating severe di

关键词： β-microseminoprotein Anticancer properties Immune modulation splice variants Promoter single nucleotide polymorphism rs10993994 Biochemical recurrence

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