Novel lncRNA AL033381.2 Promotes Hepatocellular Carcinoma Progression by Upregulating PRKRA Expression.
Novel lncRNA AL033381.2 Promotes Hepatocellular Carcinoma Progression by Upregulating PRKRA Expression.
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新型lncRNA AL033381.2通过上调PRKRA表达促进肝细胞癌进展
DOI：
10.1155/2022/1125932
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发表时间：
2022
影响因子：
--
通讯作者：
Chen Z
中科院分区：
文献类型：
--
作者：
Wang F;Zhu L;Xue Q;Tang C;Tang W;Zhang N;Dai C;Chen Z
肝细胞癌（HCC）是一种常见的恶性肿瘤，具有侵袭性和预后差的特点。越来越多的证据表明，氧化应激在致癌过程中起着至关重要的作用，而氧化应激与致癌作用之间的潜在机制尚不明确。近年来，长链非编码rna （long noncoding RNAs, lncRNAs）在癌症中的研究引起了广泛关注，并被证明参与氧化应激反应和致癌作用。然而，lncRNA AL033381.2在调节HCC发生进展中的作用尚不清楚。我们的研究目的是评估AL033381.2在HCC中可能参与氧化应激反应的潜在作用和分子机制。利用基于TCGA数据库的生物信息学分析，我们在HCC中筛选并鉴定了一个可能参与氧化应激反应的新型lncRNA AL033381.2。qRT-PCR分析显示，AL033381.2在HCC组织中表达上调。通过体外和体内实验，我们发现AL033381.2显著促进HCC的生长和转移。在机制上，采用RNA下拉实验、质谱、PathArray™和RIP来确定AL033381.2与PRKRA结合，并可能参与了AL033381.2介导的HCC细胞的致癌功能。此外，拯救实验表明，PRKRA过表达可以拯救受AL033381.2敲低影响的HCC细胞增殖、迁移和侵袭能力。此外，我们制作了一种基于纳米颗粒的siRNA递送系统，并在体内测试了其治疗效果。结果表明，纳米颗粒/AL033381.2 siRNA复合物对肿瘤的体内生长速度明显低于纳米颗粒/scramble siRNA复合物。综上所述，我们的研究结果表明，新型lncRNA AL033381.2可能通过靶向HCC中氧化应激相关基因参与氧化应激反应。AL033381.2在HCC进展中起着重要的致瘤作用，可能成为HCC诊断和治疗的新的治疗标志物。
Hepatocellular carcinoma (HCC) is a common malignant tumor that is characterized by aggressiveness and poor prognosis. Accumulating evidence indicates that oxidative stress plays a crucial role in carcinogenesis, whereas the potential mechanism between oxidative stress and carcinogenic effects remains elusive. In recent years, long noncoding RNAs (lncRNAs) in cancers have attracted extensive attention and have been shown to be involved in oxidative stress response and carcinogenesis. Nevertheless, the roles of lncRNA AL033381.2 in regulating the development and progression of HCC still remain unclear. The purpose of our study was to evaluate the potential effects and molecular mechanisms of AL033381.2 that may be involved in oxidative stress response in HCC. Using bioinformatics analyses based on the TCGA database, we screened and identified a novel lncRNA AL033381.2 in HCC, which may be involved in oxidative stress responses. qRT-PCR analysis revealed that AL033381.2 is upregulated in HCC tissues. Through in vitro and in vivo experiments, we found that AL033381.2 dramatically facilitates the growth and metastasis of HCC. Mechanistically, RNA pull-down experiments, mass spectrometry, PathArray™, and RIP were used to determine that AL033381.2 binds to PRKRA and may be involved in AL033381.2-mediated oncogenic functions in HCC cells. Moreover, rescue experiments demonstrated that PRKRA overexpression rescues the abilities of HCC cell proliferation, migration, and invasion that were affected by AL033381.2 knockdown. Furthermore, we produced a nanoparticle-based siRNA delivery system and tested its therapeutic effects in vivo. The results showed that the in vivo growth rate of the tumors treated with the nanoparticle/AL033381.2 siRNA complexes was dramatically lower than those treated with the nanoparticle/scramble siRNA complexes. Taken together, our results suggest that the novel lncRNA AL033381.2 may be involved in oxidative stress response by targeting oxidative stress-related genes in HCC. AL033381.2 plays vital oncogenic roles in HCC progression and may be a novel therapeutic marker for HCC diagnosis and treatment.
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影响因子：
4.7
作者：
Ghafouri-Fard S;Gholipour M;Hussen BM;Taheri M
通讯作者：
Taheri M
肝细胞癌肝切除术后晚期复发的危险因素、模式和结果来自中国的多中心研究
影响因子：
16.9
作者：
Xu, Xin-Fei;Xing, Hao;Yang, Tian
通讯作者：
Yang, Tian
影响因子：
4.8
作者：
Kok, Kin Hang;Ng, Ming-Him James;Jin, Dong-Yan
通讯作者：
Jin, Dong-Yan
DOI：
10.1038/s41580-020-00315-9
发表时间：
2021-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Statello L;Guo CJ;Chen LL;Huarte M
通讯作者：
Huarte M
影响因子：
8
作者：
Brahma, Manoja K.;Gilglioni, Eduardo H.;Zhou, Lang;Trepo, Eric;Chen, Pengyu;Gurzov, Esteban N.
通讯作者：
Gurzov, Esteban N.