Advances in functional genomics have led to discovery of a large group of previous uncharacterized long non-coding RNAs （IncRNAs）. Emerging evidence indicates that IncRNAs may serve as master gene regulators through...Advances in functional genomics have led to discovery of a large group of previous uncharacterized long non-coding RNAs （IncRNAs）. Emerging evidence indicates that IncRNAs may serve as master gene regulators through various mechanisms. Dysregulation of IncRNAs is often associated with a variety of human diseases including cancer. Of significant interest, recent studies suggest that IncRNAs participate in the p53 tumor suppressor regulatory network. In this review, we discuss how IncRNAs serve as p53 regulators or p53 effectors. Further characterization of these p53-associated IncRNAs in cancer will provide a better understanding of lncRNA- mediated gene regulation in the p53 pathway. As a result, IncRNAs may prove to be valuable biomarkers for cancer diagnosis or poten- tial targets for cancer therapy.展开更多
INTRODUCTIONHepatocellular carcinoma (HCC) is one of the mostcommon human malignancies worldwide[1,2], and isclosely associated with infection of HBV and HCVand contamination of aflatoxin B1[3-6]. Althoughthe molecula...INTRODUCTIONHepatocellular carcinoma (HCC) is one of the mostcommon human malignancies worldwide[1,2], and isclosely associated with infection of HBV and HCVand contamination of aflatoxin B1[3-6]. Althoughthe molecular mechanisms of hepatocarcinogenesisremain poorly understood, an increasing number ofgenetic abnormalities have been recognized[7-10],for example, the p16 gene[11,12] the p53gene[13-18], the E-cadherin gene[19], and the c-mycgene[20].展开更多
IM To investigate the risk factors of esophageal cancer (EC) in urban areas of Xi′an and to determine the association between overexpression of P53 and these risk factors.METHODS All cases (89) and controls (97) we...IM To investigate the risk factors of esophageal cancer (EC) in urban areas of Xi′an and to determine the association between overexpression of P53 and these risk factors.METHODS All cases (89) and controls (97) were permanent residents in urban areas of Xi′an, all cases of primary EC had been histologically confirmed, controls were inpatients with noncancer and nonsmokingrelated disease. Cancer tissues and tissues adjacent to the cancer of 65 cases and 24 available normal esophageal tissues of controls were detected for P53 overexpression by the immunohistochemical method.RESULTS The smoking and familial history of cancer were significantly associated with EC in Xi′an inhabitants. The laboratory assay indicated that P53 positive stain in EC was 500%(34/65) and 61%(4/65) in tissues adjacent to the cancer, but no positive stain was found in normal esophageal tissues of controls. The results showed that P53 overexpression in EC was closely related to smoking and cases with familial history of cancer.CONCLUSION Smoking and familial cancer history were important risk factors for EC, and the alteration of P53 gene may be due to smoking and inheritance factors..展开更多
Gallbladder cancer(GBC) is infrequent but most lethal biliary tract malignancy characterized by an advanced stage diagnosis and poor survival rates attributed to absence of specific symptoms and effective treatment op...Gallbladder cancer(GBC) is infrequent but most lethal biliary tract malignancy characterized by an advanced stage diagnosis and poor survival rates attributed to absence of specific symptoms and effective treatment options. These necessitate development of early prognostic/predictive markers and novel therapeutic interventions. Micro RNAs(mi RNAs) are small, noncoding RNA molecules that play a key role in tumor biology by functioning like tumor suppressor- or oncogenes and their aberrant expression are associated with the pathogenesis of several neoplasms with overwhelming clinical implications. Since mi RNA signature is tissue specific, here, we focused on current data concerning the mi RNAs abberations in GBC pathogenesis. In GBC, mi RNAs with tumor suppressor activity(mi R-135-5p, mi R-335, mi R-34 a, mi R-26 a, mi R-146b-5p, Mir-218-5p, mi R-1, mi R-145, mir-130a) were found downregulated, while those with oncogenic property(mi R-20 a, mi R-182, mir-155) were upregulated. The expression profile of mi RNAs was significantly associated with GBC prognosis and prediction, and forced over-expression/ inhibition of these mi RNAs was shown to affect tumor growth and development. Further, differential expression of mi RNAs in the blood samples of GBC patients suggest mi RNAs as promising noninvasive biomarker. Thus, mi RNAs represent potential candidate for GBC management, though many hurdles need to be overcome before mi RNAs therapy can be clinically applied to GBC prevention and treatment.展开更多
AIM:There are conflicting data about p53 function on cellular sensitivity to the cytotoxic action of 5-fluorouracil (5-FU). Therefore the objective of this study was to determine the combined effects of adenovirus-med...AIM:There are conflicting data about p53 function on cellular sensitivity to the cytotoxic action of 5-fluorouracil (5-FU). Therefore the objective of this study was to determine the combined effects of adenovirus-mediated wild-type (wt) p53 gene transfer and 5-FU chemotherapy on pancreatic cancer cells with different p53 gene status. METHODS:Human pancreatic cancer cell lines Capan-1^(p53mut), Capan-2^(p53wt),FAMPAC^(p53mut),PANC1^(p53mut),and rat pancreatic cancer cell lines AS^(p53wt) and DSL6A^(p53null) were used for in vitro studies.Following infection with different ratios of Ad- p53-particles (MOI) in combination with 5-FU,proliferation of tumor cells and apoptosis were quantified by cell proliferation assay (WST-1) and FACS (PI-staining).In addition,DSL6A syngeneic pancreatic tumor cells were inoculated subcutaneously in to Lewis rats for in vivo studies. Tumor size,apoptosis (TUNEL) and survival were determined. RESULTS:Ad-p53 gene transfer combined with 5-FU significantly inhibited tumor cell proliferation and substantially enhanced apoptosis in all four cell lines with an alteration in the p53 gene compared to those two cell lines containing wt-p53.In vivo experiments showed the most effective tumor regression in animals treated with Ad-p53 plus 5-FU.Both in vitro and in vivo analyses revealed that a sublethal dose of Ad-p53 augmented the apoptotic response induced by 5-FU. CONCLUSION:Our results suggest that Ad-p53 may synergistically enhance 5-FU-chemosensitivity most strikingly in pancreatic cancer cells lacking p53 function.These findings illustrate that the anticancer efficacy of this combination treatment is dependent on the p53 gene status of the target tumor cells.展开更多
目的采用SMART(switching mechanism at 5' end of RNA transcript)技术,快速构建高质量的人脑胶质瘤组织全长cDNA文库。方法提取多份人脑胶质瘤组织标本的总RNA,混合后处理得到纯化的mRNA,利用CDSⅢ/3'PCR引物(含SfiⅠB酶切位...目的采用SMART(switching mechanism at 5' end of RNA transcript)技术,快速构建高质量的人脑胶质瘤组织全长cDNA文库。方法提取多份人脑胶质瘤组织标本的总RNA,混合后处理得到纯化的mRNA,利用CDSⅢ/3'PCR引物(含SfiⅠB酶切位点)反转录,用SMARTⅣOligo(dT)(含SfiⅠA酶切位点)作为mRNA5'端延伸出去的模板,合成多出一段SMARTⅣOligo(dT)互补序列的cDNA第一链,进而以此序列为引物合成全长的双链cDNA。双链cDNA经SfiⅠ(A&B)酶切后克隆入经SfiⅠ酶切的λTriplEx2载体,再经噬菌体包装蛋白包装成为cDNA文库。结果获得2.4×106个重组子,重组率达100%,文库扩增后,滴度达4.5×109 pfu/ml,插入cDNA平均长度为1.2kb。结论成功构建高质量的人脑胶质瘤组织全长cDNA文库,为进一步筛选、克隆人脑胶质瘤抑癌基因及特异性表达基因奠定基础。展开更多
Deletion of chromosome 6q is frequent in breast cancer, and the deletion often involves a region in 6q 14-q 16. At present, however, the underlying tumor suppressor gene has not been established. Based on a recent stu...Deletion of chromosome 6q is frequent in breast cancer, and the deletion often involves a region in 6q 14-q 16. At present, however, the underlying tumor suppressor gene has not been established. Based on a recent study identifying snoRNA U50 as a candidate for the 6q14-16 tumor suppressor gene in prostate cancer, we investigated whether U50 is also involved in breast cancer. PCR-based approaches showed that U50 underwent frequent genomic deletion and transcriptional downregulation in cell lines derived from breast cancer. Mutation screening identified the same 2-bp deletion of U50 as in prostate cancer in both cell lines and primary tumors from breast cancer, and the deletion was both somatic and in germline. Genotyping of a cohort of breast cancer cases and controls for the mutation demonstrated that, while homozygous genotype of the mutation was rare, its heterozygous genotype occurred more frequently in women with breast cancer. Functionally, re-expression of U50 resulted in the inhibition of colony formation in breast cancer cell lines. These results suggest that noncoding snoRNA U50 plays a role in the development and/or progression of breast cancer.展开更多
文摘Advances in functional genomics have led to discovery of a large group of previous uncharacterized long non-coding RNAs （IncRNAs）. Emerging evidence indicates that IncRNAs may serve as master gene regulators through various mechanisms. Dysregulation of IncRNAs is often associated with a variety of human diseases including cancer. Of significant interest, recent studies suggest that IncRNAs participate in the p53 tumor suppressor regulatory network. In this review, we discuss how IncRNAs serve as p53 regulators or p53 effectors. Further characterization of these p53-associated IncRNAs in cancer will provide a better understanding of lncRNA- mediated gene regulation in the p53 pathway. As a result, IncRNAs may prove to be valuable biomarkers for cancer diagnosis or poten- tial targets for cancer therapy.
基金Project supported partly by the National Natural Science Foundation of China, No. 39870344
文摘INTRODUCTIONHepatocellular carcinoma (HCC) is one of the mostcommon human malignancies worldwide[1,2], and isclosely associated with infection of HBV and HCVand contamination of aflatoxin B1[3-6]. Althoughthe molecular mechanisms of hepatocarcinogenesisremain poorly understood, an increasing number ofgenetic abnormalities have been recognized[7-10],for example, the p16 gene[11,12] the p53gene[13-18], the E-cadherin gene[19], and the c-mycgene[20].
文摘IM To investigate the risk factors of esophageal cancer (EC) in urban areas of Xi′an and to determine the association between overexpression of P53 and these risk factors.METHODS All cases (89) and controls (97) were permanent residents in urban areas of Xi′an, all cases of primary EC had been histologically confirmed, controls were inpatients with noncancer and nonsmokingrelated disease. Cancer tissues and tissues adjacent to the cancer of 65 cases and 24 available normal esophageal tissues of controls were detected for P53 overexpression by the immunohistochemical method.RESULTS The smoking and familial history of cancer were significantly associated with EC in Xi′an inhabitants. The laboratory assay indicated that P53 positive stain in EC was 500%(34/65) and 61%(4/65) in tissues adjacent to the cancer, but no positive stain was found in normal esophageal tissues of controls. The results showed that P53 overexpression in EC was closely related to smoking and cases with familial history of cancer.CONCLUSION Smoking and familial cancer history were important risk factors for EC, and the alteration of P53 gene may be due to smoking and inheritance factors..
文摘Gallbladder cancer(GBC) is infrequent but most lethal biliary tract malignancy characterized by an advanced stage diagnosis and poor survival rates attributed to absence of specific symptoms and effective treatment options. These necessitate development of early prognostic/predictive markers and novel therapeutic interventions. Micro RNAs(mi RNAs) are small, noncoding RNA molecules that play a key role in tumor biology by functioning like tumor suppressor- or oncogenes and their aberrant expression are associated with the pathogenesis of several neoplasms with overwhelming clinical implications. Since mi RNA signature is tissue specific, here, we focused on current data concerning the mi RNAs abberations in GBC pathogenesis. In GBC, mi RNAs with tumor suppressor activity(mi R-135-5p, mi R-335, mi R-34 a, mi R-26 a, mi R-146b-5p, Mir-218-5p, mi R-1, mi R-145, mir-130a) were found downregulated, while those with oncogenic property(mi R-20 a, mi R-182, mir-155) were upregulated. The expression profile of mi RNAs was significantly associated with GBC prognosis and prediction, and forced over-expression/ inhibition of these mi RNAs was shown to affect tumor growth and development. Further, differential expression of mi RNAs in the blood samples of GBC patients suggest mi RNAs as promising noninvasive biomarker. Thus, mi RNAs represent potential candidate for GBC management, though many hurdles need to be overcome before mi RNAs therapy can be clinically applied to GBC prevention and treatment.
文摘AIM:There are conflicting data about p53 function on cellular sensitivity to the cytotoxic action of 5-fluorouracil (5-FU). Therefore the objective of this study was to determine the combined effects of adenovirus-mediated wild-type (wt) p53 gene transfer and 5-FU chemotherapy on pancreatic cancer cells with different p53 gene status. METHODS:Human pancreatic cancer cell lines Capan-1^(p53mut), Capan-2^(p53wt),FAMPAC^(p53mut),PANC1^(p53mut),and rat pancreatic cancer cell lines AS^(p53wt) and DSL6A^(p53null) were used for in vitro studies.Following infection with different ratios of Ad- p53-particles (MOI) in combination with 5-FU,proliferation of tumor cells and apoptosis were quantified by cell proliferation assay (WST-1) and FACS (PI-staining).In addition,DSL6A syngeneic pancreatic tumor cells were inoculated subcutaneously in to Lewis rats for in vivo studies. Tumor size,apoptosis (TUNEL) and survival were determined. RESULTS:Ad-p53 gene transfer combined with 5-FU significantly inhibited tumor cell proliferation and substantially enhanced apoptosis in all four cell lines with an alteration in the p53 gene compared to those two cell lines containing wt-p53.In vivo experiments showed the most effective tumor regression in animals treated with Ad-p53 plus 5-FU.Both in vitro and in vivo analyses revealed that a sublethal dose of Ad-p53 augmented the apoptotic response induced by 5-FU. CONCLUSION:Our results suggest that Ad-p53 may synergistically enhance 5-FU-chemosensitivity most strikingly in pancreatic cancer cells lacking p53 function.These findings illustrate that the anticancer efficacy of this combination treatment is dependent on the p53 gene status of the target tumor cells.
文摘目的采用SMART(switching mechanism at 5' end of RNA transcript)技术,快速构建高质量的人脑胶质瘤组织全长cDNA文库。方法提取多份人脑胶质瘤组织标本的总RNA,混合后处理得到纯化的mRNA,利用CDSⅢ/3'PCR引物(含SfiⅠB酶切位点)反转录,用SMARTⅣOligo(dT)(含SfiⅠA酶切位点)作为mRNA5'端延伸出去的模板,合成多出一段SMARTⅣOligo(dT)互补序列的cDNA第一链,进而以此序列为引物合成全长的双链cDNA。双链cDNA经SfiⅠ(A&B)酶切后克隆入经SfiⅠ酶切的λTriplEx2载体,再经噬菌体包装蛋白包装成为cDNA文库。结果获得2.4×106个重组子,重组率达100%,文库扩增后,滴度达4.5×109 pfu/ml,插入cDNA平均长度为1.2kb。结论成功构建高质量的人脑胶质瘤组织全长cDNA文库,为进一步筛选、克隆人脑胶质瘤抑癌基因及特异性表达基因奠定基础。
基金supported in part by a grant from the National Cancer Institute,USA (No. R01CA085560)
文摘Deletion of chromosome 6q is frequent in breast cancer, and the deletion often involves a region in 6q 14-q 16. At present, however, the underlying tumor suppressor gene has not been established. Based on a recent study identifying snoRNA U50 as a candidate for the 6q14-16 tumor suppressor gene in prostate cancer, we investigated whether U50 is also involved in breast cancer. PCR-based approaches showed that U50 underwent frequent genomic deletion and transcriptional downregulation in cell lines derived from breast cancer. Mutation screening identified the same 2-bp deletion of U50 as in prostate cancer in both cell lines and primary tumors from breast cancer, and the deletion was both somatic and in germline. Genotyping of a cohort of breast cancer cases and controls for the mutation demonstrated that, while homozygous genotype of the mutation was rare, its heterozygous genotype occurred more frequently in women with breast cancer. Functionally, re-expression of U50 resulted in the inhibition of colony formation in breast cancer cell lines. These results suggest that noncoding snoRNA U50 plays a role in the development and/or progression of breast cancer.
