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LncRNA C9orf139 can regulate the growth of pancreatic cancer by mediating the miR-663a/Sox12 axis 被引量:4
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作者 Jin-Nian Ge Di Yan +1 位作者 Chun-Lin Ge Min-Jie Wei 《World Journal of Gastrointestinal Oncology》 SCIE CAS 2020年第11期1272-1287,共16页
BACKGROUND Recent studies have proved the important role of many oncogenic long noncoding RNAs(lncRNAs) in the progression of pancreatic cancer, but little is known about the mechanisms of tumor suppression in pancrea... BACKGROUND Recent studies have proved the important role of many oncogenic long noncoding RNAs(lncRNAs) in the progression of pancreatic cancer, but little is known about the mechanisms of tumor suppression in pancreatic cancer.AIM To evaluate the function of tumor suppressor lncRNA C9orf139 in pancreatic cancer progression and to study the underlying mechanism.METHODS We assigned 54 patients with pancreatic ductal adenocarcinoma treated at our hospital to the patient group and 30 normal subjects undergoing physical examination to the control group. RT-qPCR was used to measure the relative expression of C9orf139 in the tissue and serum of patients, in an attempt to investigate the prognostic value of C9orf139 in pancreatic cancer patients. The luciferase reporter gene assay was performed to determine the interaction between C9orf139 and miR-663 a. The biological function of C9orf139 was assessed by in vitro assays and in vivo subcutaneous tumor formation tests in animal models. To figure out the molecular mechanism of C9orf139 to act on miR-663 a/Sox12, RNA pull-down, Western blot assay, RNA immunoprecipitation assay, and co-immunoprecipitation assay were performed.RESULTS C9orf139 level significantly increased in the tissue and serum of patients, which had clinical diagnostic value for pancreatic cancer. Patients with high C9orf139 expression had a higher risk of progressing to stage Ⅲ + Ⅳ, lymph node metastasis, and poor differentiation. Cox regression analysis suggested that C9orf139, tumor-node-metastasis stage, and lymph node metastasis were independent prognostic factors in patients. The underlying mechanism of C9orf139 was that it promoted the growth of pancreatic cancer cells by modulating the miR-663 a/Sox12 axis.CONCLUSION C9orf139 is highly expressed in pancreatic cancer, qualified to be used as a potential diagnostic and prognostic marker for pancreatic cancer. Its promotion of pancreatic cancer cell growth is achieved by mediating the miR-663 a/Sox12 axis. 展开更多
关键词 c9orf139 miR-663a Sox12 Pancreatic cancer Prognosis Tumor formation in nude mice
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长链非编码RNA C9ORF139靶向miR-24-3P/TAOK1调控急性髓系白血病细胞增殖的作用和机制 被引量:2
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作者 秦伟 蔡晓辉 +6 位作者 韩文敏 卢绪章 陈梅玉 贾祝霞 刘洁 肖溶 钱思轩 《中华医学杂志》 CAS CSCD 北大核心 2022年第8期576-583,共8页
目的:探讨长链非编码RNA(lncRNA)C9ORF139靶向微小RNA(miR)-24-3P/TAOK1调控急性髓系白血病(AML)细胞增殖的作用和机制。方法:AML细胞株(人急性早幼粒白血病细胞株HL-60以及人单核白血病细胞株THP-1)购自中国科学院,分为4组:A组为阴性对... 目的:探讨长链非编码RNA(lncRNA)C9ORF139靶向微小RNA(miR)-24-3P/TAOK1调控急性髓系白血病(AML)细胞增殖的作用和机制。方法:AML细胞株(人急性早幼粒白血病细胞株HL-60以及人单核白血病细胞株THP-1)购自中国科学院,分为4组:A组为阴性对照(siNC)组,B组为干扰C9ORF139(siC9ORF139)组,C组为siC9ORF139+miR-24-3P抑制剂组,D组为miR-24-3P+TAOK1过表达(oe-TAOK1)组。采用实时荧光定量逆转录(qRT)-PCR检测4组AML细胞株HL-60、THP-1中的表达水平。细胞计数试剂盒-8(CCK8)法检测细胞增殖,流式细胞仪分析细胞的凋亡情况,Transwell实验检测4组细胞的迁移、侵袭能力,Western印迹法检测p-丝氨酸/苏氨酸激酶(p-raf)、p-丝裂原活化蛋白激酶(p-MEK)、p-细胞外调节蛋白激酶(p-ERK)表达。构建荧光素酶报告基因质粒,验证C9ORF139、miR-24-3P、TAOK1的结合能力。裸鼠皮下肿瘤细胞接种分为HL-60(A组)和HL-60(B组)。结果:敲减细胞中C9ORF139基因并培养120 h后,在HL-60及THP-1细胞中,B组细胞增殖能力(0.62±0.02、0.82±0.02)、迁移能力(0.22±0.03、0.05±0.01)、侵袭能力(0.20±0.02、0.13±0.03)均低于A组(1.30±0.02、1.83±0.07;0.99±0.02、0.99±0.02;1.00±0.01、1.00±0.01)(均 P<0.05)。共转染miR-24-3抑制剂后,细胞增殖能力、迁移能力、侵袭能力均高于B组(均 P<0.05)。共转染miR-24-3P与oe-TAOK1质粒后,细胞增殖能力、迁移能力、侵袭能力均高于B组(均 P<0.05)。当干扰细胞中C9ORF139基因后,与A组凋亡水平(0.31±0.27、2.49±0.33)相比,B组(28.56±8.07、17.74±1.91)均较高(均 P<0.05);当共转染miR-24-3P抑制剂后,C组细胞凋亡水平(2.34±0.09、3.06±0.06)均低于B组(均 P<0.05);在共转染miR-24-3P与oe-TAOK1质粒组中,D组细胞凋亡水平(2.16±1.29、4.80±0.37)均低于B组(均 P<0.05)。在HL-60、THP-1细胞中,当C9ORF139未突变时,miR-24-3P组荧光素酶活性均低于miR-NC组(均 P<0.05)。当C9ORF139序列中与miR-24-3P结合位点突变后,miR-24-3P组荧光素酶活性与miR-NC组差异无统计学意义( P>0.05)。当TAOK1未突变时,miR-24-3P组荧光素酶活性低于miR-NC组( P<0.05);当TAOK1序列中与miR-24-3P结合位点突变后,miR-24-3P组荧光素酶活性与miR-NC组差异无统计学意义( P>0.05)。当干扰HL-60细胞中C9ORF139基因并培养72 h后,B组Raf、MEK及ERK分子磷酸化表达水平均低于A组(均 P<0.05)。第14天,A组肿瘤体积高于B组[(284.49±57.61)比(125.70±18.64)mm 3, P=0.017]。HL-60 A组肿瘤重量高于B组[(847.80±159.36)比(408.40±113.16)mg, P=0.001]。 结论:lncRNA C9ORF139通过调控miR-24-3P上调TAOK1促进AML细胞的增殖、侵袭、迁移,C9ORF139表达具有促进AML裸鼠皮下肿瘤生长的作用。 展开更多
关键词 白血病 髓样 急性 细胞增殖 细胞凋亡 长链非编码RNA c9orf139 微小RNA-24-3P
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