目的:探讨候选抑癌基因RASSF6在胃癌组织中的表达及其与临床病理特征的关系。方法:采用组织微阵列技术,通过免疫组化SP法检测100例胃癌组织和癌旁正常组织中RASSF6的表达,实时荧光定量RT-PCR和Western blot法检测20例新鲜胃癌组织和癌...目的:探讨候选抑癌基因RASSF6在胃癌组织中的表达及其与临床病理特征的关系。方法:采用组织微阵列技术,通过免疫组化SP法检测100例胃癌组织和癌旁正常组织中RASSF6的表达,实时荧光定量RT-PCR和Western blot法检测20例新鲜胃癌组织和癌旁正常组织中RASSF6m RNA及蛋白的表达情况。结果:(1)胃癌组织中RASSF6阳性表达率明显低于癌旁正常组织(31.0%vs 76.0%,P<0.05),胃癌组织中RASSF6m RNA和蛋白表达水平明显低于癌旁正常组织(3.949±0.816 vs 4.522±0.685和1.589±2.237 vs 5.723±1.939,P均<0.05)。(2)RASSF6在胃癌组织中的表达与胃癌分化程度、浸润深度、淋巴结转移及胃癌分期差异均有统计学意义(P均<0.05)。结论:RASSF6可能是胃癌中新的抑癌基因,其表达缺失与胃癌的发生和进展有关。展开更多
RAS相关结构域家族(Ras Association Domain Family,RASSFs)由10个成员组成,参与不同的细胞内机制如凋亡、细胞周期控制、微管稳定性等,一些家族成员表现出肿瘤抑制功能。目前发现RASSF6在肺癌、宫颈癌等实体瘤中表达下调,可能与肿瘤形...RAS相关结构域家族(Ras Association Domain Family,RASSFs)由10个成员组成,参与不同的细胞内机制如凋亡、细胞周期控制、微管稳定性等,一些家族成员表现出肿瘤抑制功能。目前发现RASSF6在肺癌、宫颈癌等实体瘤中表达下调,可能与肿瘤形成有关,并可作为肿瘤治疗的潜在靶点。本文就RASSF6与肿瘤的研究进展进行综述。展开更多
Ras-association(RA) domain family number 6(RASSF6) is a member of the Ras-association domain protein family.It is epigenetically inactive and negatively regulates the malignant progression of some tumors.However,its p...Ras-association(RA) domain family number 6(RASSF6) is a member of the Ras-association domain protein family.It is epigenetically inactive and negatively regulates the malignant progression of some tumors.However,its precise role in esophageal squamous cell carcinoma(ESCC) has not been reported.In this study,we performed immunohistochemistry(IHC) assay.The results show that RASSF6 is upregulated in ESCC and that the elevated expression level of RASSF6 is associated with lymph node metastasis and poor survival of ESCC patients.Consistent with the clinical obse rvations,the upregulation of RASSF6 greatly promotes ESCC cell proliferation,migration and invasion as well as the cell cycle transition to Gl/S phase in vitro.According to models in vivo,the downregulation of RASSF6 considerably inhibits ESCC tumor growth and lung metastasis.Mechanistically,RASSF6 negatively regulates the tumor suppressor tripartite-motif-containing protein 16(TRIM16) by promoting its ubiquitination-dependent degradation and eventually activates pathways associated with the cell cycle and epithelialmesenchymal transition(EMT).Together,these results indicate that the RASSF6-TRIM16 axis is a key effector in ESCC progression and that RASSF6 serves as a potential target for the treatment of ESCC.展开更多
AIM:To analyze RASSF6 expression in pancreatic ductal adenocarcinoma(PDAC) and to determine whether RASSF6 has an independent prognostic value in PDAC.METHODS:We studied RASSF6 expression in 96 histologically confirme...AIM:To analyze RASSF6 expression in pancreatic ductal adenocarcinoma(PDAC) and to determine whether RASSF6 has an independent prognostic value in PDAC.METHODS:We studied RASSF6 expression in 96 histologically confirmed PDAC samples and 20 chronic pancreatitis specimens using immunohistochemistry and real-time quantitative reverse transcription-PCR.PDAC issues were then classified as RASSF6 strongly positive,weakly positive or negative.RASSF6 mR NA and protein expression in PDAC samples with strong positive staining was further evaluated using real-time PCR and Western blot analysis.Lastly,correlations between RASSF6 staining and patients' clinicopathological variables and outcomes were assessed.RESULTS:RASSF6 was negatively expressed in 51(53.1%) PDAC samples,weakly positively expressed in 29(30.2%) and strongly positively expressed in16(16.7%),while its expression was much higher in para-tumor tissues and chronic pancreatitis tissues.Positive relationships between RASSF6 expression and T-stage(P = 0.047) and perineural invasion(P = 0.026) were observed.The median survival time of strongly and weakly positive and negative RASSF6 staining groups was 33 mo,15 mo and 11 mo,respectively.Cox multivariate analysis indicated that RASSF6 was an independent prognostic indicator of overall survival in patients with PDAC.A survival curve analysis revealed that increased RASSF6 expression was correlated with better overall survival(P = 0.009).CONCLUSION:RASSF6 expression is an independent biomarker of an unfavorable prognosis in patients with PDAC.展开更多
目的干扰素是晚期肾癌的常用治疗药物,但多数患者最终对干扰素产生耐药导致治疗失败。本研究探讨RAS结构相关蛋白(ras association domain-containing protein 6,RASSF6)调控肾癌细胞对干扰素-α敏感性的影响及分子机制。方法利用慢病...目的干扰素是晚期肾癌的常用治疗药物,但多数患者最终对干扰素产生耐药导致治疗失败。本研究探讨RAS结构相关蛋白(ras association domain-containing protein 6,RASSF6)调控肾癌细胞对干扰素-α敏感性的影响及分子机制。方法利用慢病毒建立稳定过表达RASSF6的786-O细胞(786-O-RF6)及其空白对照细胞(786-O-Vec),利用MTS法测定细胞存活率,流式细胞术检测细胞凋亡,通过免疫印迹法检测Bax蛋白表达水平及JNK通路核心激酶磷酸化水平。结果过表达RASSF6减少786-O细胞存活率,1×105 IU/L IFN:786-O-Vec组存活率为(87.7±4.8)%,786-O-RF6组为(60.3±15.5)%,P=0.042;2×105 IU/L IFN:786-O-Vec组细胞存活率为(81.4±6.0)%,786-O-RF6组为(50.4±11.0)%,P=0.023)。786-O细胞中过表达RASSF6增加细胞凋亡,过表达RASSF6细胞凋亡率为(57.3±15.6)%,对照组为(14.8±2.1)%,P=0.01。过表达RASSF6增加凋亡因子Bax表达及JNK磷酸化水平。结论过表达RASSF6逆转肾癌细胞对干扰素-α的抵抗,提示RASSF6通过激活JNK/SAPK通路增加干扰素-α引起的凋亡,抑制细胞存活。展开更多
文摘目的:探讨候选抑癌基因RASSF6在胃癌组织中的表达及其与临床病理特征的关系。方法:采用组织微阵列技术,通过免疫组化SP法检测100例胃癌组织和癌旁正常组织中RASSF6的表达,实时荧光定量RT-PCR和Western blot法检测20例新鲜胃癌组织和癌旁正常组织中RASSF6m RNA及蛋白的表达情况。结果:(1)胃癌组织中RASSF6阳性表达率明显低于癌旁正常组织(31.0%vs 76.0%,P<0.05),胃癌组织中RASSF6m RNA和蛋白表达水平明显低于癌旁正常组织(3.949±0.816 vs 4.522±0.685和1.589±2.237 vs 5.723±1.939,P均<0.05)。(2)RASSF6在胃癌组织中的表达与胃癌分化程度、浸润深度、淋巴结转移及胃癌分期差异均有统计学意义(P均<0.05)。结论:RASSF6可能是胃癌中新的抑癌基因,其表达缺失与胃癌的发生和进展有关。
文摘RAS相关结构域家族(Ras Association Domain Family,RASSFs)由10个成员组成,参与不同的细胞内机制如凋亡、细胞周期控制、微管稳定性等,一些家族成员表现出肿瘤抑制功能。目前发现RASSF6在肺癌、宫颈癌等实体瘤中表达下调,可能与肿瘤形成有关,并可作为肿瘤治疗的潜在靶点。本文就RASSF6与肿瘤的研究进展进行综述。
基金supported by funding from the National Key Research and Development Program of China (No. 2016YFA0500303)the National Natural Science Foundation of China(No.81872398)+5 种基金CAMS Innovation Fund for Medical Sciences (CIFMSNo.2016-12M-1-001)a grant from Medical Epigenetics Research Center,Chinese Medical Sciences(2019PT310017)National Basic Research Program of China(No.2015CB553904)PUMC Youth Fund(No.3332018066)the National Key R&D Program of China(2018YFC1313101)
文摘Ras-association(RA) domain family number 6(RASSF6) is a member of the Ras-association domain protein family.It is epigenetically inactive and negatively regulates the malignant progression of some tumors.However,its precise role in esophageal squamous cell carcinoma(ESCC) has not been reported.In this study,we performed immunohistochemistry(IHC) assay.The results show that RASSF6 is upregulated in ESCC and that the elevated expression level of RASSF6 is associated with lymph node metastasis and poor survival of ESCC patients.Consistent with the clinical obse rvations,the upregulation of RASSF6 greatly promotes ESCC cell proliferation,migration and invasion as well as the cell cycle transition to Gl/S phase in vitro.According to models in vivo,the downregulation of RASSF6 considerably inhibits ESCC tumor growth and lung metastasis.Mechanistically,RASSF6 negatively regulates the tumor suppressor tripartite-motif-containing protein 16(TRIM16) by promoting its ubiquitination-dependent degradation and eventually activates pathways associated with the cell cycle and epithelialmesenchymal transition(EMT).Together,these results indicate that the RASSF6-TRIM16 axis is a key effector in ESCC progression and that RASSF6 serves as a potential target for the treatment of ESCC.
文摘AIM:To analyze RASSF6 expression in pancreatic ductal adenocarcinoma(PDAC) and to determine whether RASSF6 has an independent prognostic value in PDAC.METHODS:We studied RASSF6 expression in 96 histologically confirmed PDAC samples and 20 chronic pancreatitis specimens using immunohistochemistry and real-time quantitative reverse transcription-PCR.PDAC issues were then classified as RASSF6 strongly positive,weakly positive or negative.RASSF6 mR NA and protein expression in PDAC samples with strong positive staining was further evaluated using real-time PCR and Western blot analysis.Lastly,correlations between RASSF6 staining and patients' clinicopathological variables and outcomes were assessed.RESULTS:RASSF6 was negatively expressed in 51(53.1%) PDAC samples,weakly positively expressed in 29(30.2%) and strongly positively expressed in16(16.7%),while its expression was much higher in para-tumor tissues and chronic pancreatitis tissues.Positive relationships between RASSF6 expression and T-stage(P = 0.047) and perineural invasion(P = 0.026) were observed.The median survival time of strongly and weakly positive and negative RASSF6 staining groups was 33 mo,15 mo and 11 mo,respectively.Cox multivariate analysis indicated that RASSF6 was an independent prognostic indicator of overall survival in patients with PDAC.A survival curve analysis revealed that increased RASSF6 expression was correlated with better overall survival(P = 0.009).CONCLUSION:RASSF6 expression is an independent biomarker of an unfavorable prognosis in patients with PDAC.
文摘目的干扰素是晚期肾癌的常用治疗药物,但多数患者最终对干扰素产生耐药导致治疗失败。本研究探讨RAS结构相关蛋白(ras association domain-containing protein 6,RASSF6)调控肾癌细胞对干扰素-α敏感性的影响及分子机制。方法利用慢病毒建立稳定过表达RASSF6的786-O细胞(786-O-RF6)及其空白对照细胞(786-O-Vec),利用MTS法测定细胞存活率,流式细胞术检测细胞凋亡,通过免疫印迹法检测Bax蛋白表达水平及JNK通路核心激酶磷酸化水平。结果过表达RASSF6减少786-O细胞存活率,1×105 IU/L IFN:786-O-Vec组存活率为(87.7±4.8)%,786-O-RF6组为(60.3±15.5)%,P=0.042;2×105 IU/L IFN:786-O-Vec组细胞存活率为(81.4±6.0)%,786-O-RF6组为(50.4±11.0)%,P=0.023)。786-O细胞中过表达RASSF6增加细胞凋亡,过表达RASSF6细胞凋亡率为(57.3±15.6)%,对照组为(14.8±2.1)%,P=0.01。过表达RASSF6增加凋亡因子Bax表达及JNK磷酸化水平。结论过表达RASSF6逆转肾癌细胞对干扰素-α的抵抗,提示RASSF6通过激活JNK/SAPK通路增加干扰素-α引起的凋亡,抑制细胞存活。
