Oncogene:去势抵抗性前列腺癌中环状RNAs能够增加雄激素受体多样性

2019-08-25 AlexYang MedSci原创

环状RNAs(circRNAs)表达的下调与各种人类的疾病相关,包括了许多类型的癌症。尽管环状RNAs与癌症的联系不断的增加,但是circRNAs在去势抵抗性前列腺癌中的特征分析有限,该类型的癌症也是前列腺癌死亡率的主要原因。最近,有研究人员在47个转移去势抵抗性前列腺癌样本中进行了外显子捕获RNA-seq分析,并在人源性异种移植(PDXs)和细胞模型中进行了核糖耗竭和RNase RRNA序列测定

环状RNAs(circRNAs)表达的下调与各种人类的疾病相关,包括了许多类型的癌症。尽管环状RNAs与癌症的联系不断的增加,但是circRNAs在去势抵抗性前列腺癌中的特征分析有限,该类型的癌症也是前列腺癌死亡率的主要原因。

最近,有研究人员在47个转移去势抵抗性前列腺癌样本中进行了外显子捕获RNA-seq分析,并在人源性异种移植(PDXs)和细胞模型中进行了核糖耗竭和RNase RRNA序列测定。研究鉴定了13个来源于关键前列腺癌驱使基因-雄激素受体的circRNAs。他们确定和分析了4种丰度最高和临床相关的AR circRNAs。这些circRNAs的表达在PDXs的去势抵抗性恶化中表达上调。该上调并非由于circRNAs形成的增加。相反,在临床样本和PDXs中,AR circRNAs的水平与线性AR转录本(AR和AR变体)强烈相关,表明了存在一种调控转录机制。在培养的细胞中,雄激素能够抑制这些AR circRNAs和线性AR转录本的表达,且上述抑制能够通过抗雄激素物质减弱。通过细胞核/质分离和RNA原位杂交实验,研究人员阐释了这些AR circRNAs在细胞质中定位明显,表明了很可能在细胞质中行使功能。

最后,研究人员指出,他们的研究是首次综合的鉴定了来源于AR基因的circRNAs,并且可能这些AR circRNAs可作为AR/AR变体表达和去势抵抗性前列腺癌恶化的可替代标记。

原始出处:

Subing Cao, Tianfang Ma, Nathan Ungerleider et al. Circular RNAs add diversity to androgen receptor isoform repertoire in castration-resistant prostate cancer. Oncogene. 13 Aug 2019

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    2020-01-16 yige2012
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    2020-04-04 dzx0922889
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    2020-02-27 cy0324
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    2019-08-27 zsyan
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    2019-08-25 misszhang

    前列腺癌相关研究,学习了,谢谢梅斯

    0

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【1】Sci Rep:转移前列腺癌中HOXB13同源异型盒基因能够调控有丝分裂蛋白激酶互作网络 HOXB13是一个同源异型盒转录因子,并且与根治性前列腺切除术后复发有关。虽然HOXB13能够以环境依赖的方式来调控雄激素受体(AR)功能,它在前列腺癌(PC)转移中的关键影响仍旧大部分未知。最近,有研究人员为了鉴定转移性PCs中HOXB13的转录靶标,在人类前列腺肿瘤特异性AR结合位点附

Prostate Cancer P D:使用68Ga-PET/CT PSMA确定生化复发前列腺癌疾病模式研究

68Ga-PET/CT PSM扫描已经越来越多用于生化复发疾病阶段分析。放射治疗后复发疾病的早期鉴定对做出合适的早期挽救性治疗是非常重要的,并且能够改善预后。最近,有研究人员鉴定了与放射治疗后PSA水平相关的可疑前列腺癌复发的模式,尤其是那些低于公认的Phoenix定义的PSA失败水平(PSA nadir?+2)的患者。研究是一个回顾性的单中心群体研究,包括了连续性的男性患者,时间为2014年7月

Sci Rep:维生素E在前列腺癌中的致癌作用研究

许多的基础研究和观察性研究表明了维生素E具有癌症预防活性,但是大规模的人类干预试验产出的结果却让人们很失望,实际结果表明了前列腺癌的发生率更高,并且潜在的增加风险的机制仍旧不清楚。最近,有研究人员通过体外和体内试验阐释了维生素E能够对致癌生物激活酶和助氧状态产生明显的影响,从而促进DNA损伤和细胞转化频率。首先,研究人员发现维生素E在人类前列腺上皮RWPE-1细胞系中具有明显上调各种阶段I细胞色素

Cell Death & Disease:过剩的hepsin蛋白酶水解活性能够抑制致瘤信号和诱导ER应激和细胞自噬

丝氨酸蛋白酶hepsin在人类前列腺癌(PCa)中经常过表达,并且与基质降解和PCa的恶化相关。有趣的是,hepsin的低表达与不同癌症类型中不良的生存相关,hepsin转基因的过表达能够导致各种癌症细胞活力的丧失。最近,有研究人员通过比较PCa细胞系PC-3同基因转染产生的诱导型野生型hepsin(HPN)过表达细胞系与蛋白酶缺陷突变体HPNS353A细胞系,阐释了hepsin调控的肿瘤副作用影

盘点:前列腺癌与治疗进展

【1】Prostate Cancer P D:去势敏感性前列腺癌中醋酸阿比特龙与多烯紫杉醇治疗成本效益分析 https://www.nature.com/articles/s41391-019-0161-2一些随机对照试验(RCTs)表明了在雄激素阻断治疗(ADT)中加入醋酸阿比特龙(AA)或者多烯紫杉醇(D)能够改善转移去势敏感性前列腺癌患者(mCSPC)的生存。然而,这些治疗选择的成本效益

Oncogene:肿瘤抑制因子Tp53的缺失能够增强雄激素受体接到的致瘤转化和肿瘤发展

之前人类前列腺癌的基因组分析阐释了AR基因放大和TP53变异是晚期前列腺癌中最为常见的变异。然而,这些双重遗传变异在前列腺致瘤中的生物学作用仍旧未知。另外,也没有相关的生物学模型能够用于评估这些遗传异常的分子机制。最近,有研究人员报道了一个小鼠模型,该模型AR表达量提高且同时Trp53缺失,从而来模拟人类前列腺癌细胞。研究发现,与只有AR转基因小鼠相比,这些小鼠模型的高等级前列腺内上皮瘤起始更早并