解读参与索拉费尼布耐药性的非编码RNAs的作用
FanJing Jing1, YunYan Shi1, Dong Jiang2
1Department of Clinical Pharmacy, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266003, PR China.
Heliyon
|April 22, 2024
概括
在晚期肝细胞癌 (HCC) 中对索拉费尼布耐药性的研究使用了全转录组测序. 研究人员确定了与代谢重编程和上皮-介质细胞转换 (EMT) 相关的新型非编码RNA网络,为HCC治疗提供了新的治疗点.
科学领域:
- 基因组学就是基因组学.
- 分子生物学分子生物学
- 在瘤学瘤学.
背景情况:
- 索拉芬尼是晚期肝细胞癌 (HCC) 的关键治疗方法.
- 对索拉费尼布的耐药性显著限制了它在HCC患者的临床疗效.
- 了解sorafenib耐药性的分子机制对于开发有效疗法至关重要.
研究的目的:
- 研究非编码RNAs (ncRNAs) 在HCC中索拉芬尼抗性的作用.
- 在抗索拉芬尼布的HCC细胞中识别差异表达的ncRNAs (DENs) 和它们的基因.
- 构建监管网络 (lncRNA-miRNA-mRNA和circRNA-miRNA-mRNA) 作为索拉费尼布耐药性的基础.
主要方法:
- 整个转录组测序 (WTS) 在抗索拉芬尼布和亲属HCC细胞系 (SMMC7721/S和Huh7/S) 上进行.
- 鉴定出差异表达的ncRNA (长非编码RNA,圆形RNA,微RNA) 和mRNA.
- 使用生物信息学工具 (miRanda,RNAhybrid) 预测了DEN的目标基因,并与WTS数据集成.
- 使用Cytoscape软件构建了ceRNA网络.
主要成果:
- 在两种耐药细胞系中确定了几种差异表达的lncRNA,circRNA和miRNA.
- 新的lncRNA-miRNA-mRNA和circRNA-miRNA-mRNA网络被构建,包括具体的例子,如MED17-203-miRNA-mRNA和circ_0002874-miR-27a-5p-mRNA.
- 这些网络可能通过PPAR,HIF-1,Hippo和TGF-β信号通路参与代谢重编程.
- 该circ_0002874-miR-27a-5p-mRNA网络也与TGF-β信号传递和上皮层-介质细胞过渡 (EMT) 有关.
结论:
- 新的ncRNA调节网络在HCC中对索拉芬尼布耐药性起着重要作用.
- 这些网络涉及代谢重编程和EMT,这是HCC进展和药物耐药性的关键过程.
- 这些发现为开发针对索拉芬尼布耐药HCC的向治疗提供了理论基础.
更多相关视频
07:23Dual CRISPR-Interference Strategy for Targeting Synthetic Lethal Interactions Between Non-Coding RNAs in Cancer Cells
Published on: May 30, 2025
288
12:13Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
Published on: November 19, 2019
6.8K
相关概念视频
lncRNA - Long Non-coding RNAs
8.6K
In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
8.6K
Treatment Resistant Cancers
3.3K
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.3K
Types of RNA
5.8K
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in regulating gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA Performs Diverse...
RNA Performs Diverse...
5.8K
MicroRNAs
3.0K
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
3.0K
siRNA - Small Interfering RNAs
16.7K
Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
16.7K
Experimental RNAi
6.1K
RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
6.1K
