长链非编码RNA HIF1A-AS2作为一种癌基因调节宫颈癌的恶性表型。
lncRNA HIF1A-AS2 acts as an oncogene to regulate malignant phenotypes in cervical cancer.
作者信息
Liu Yang, Zhang Yunyan, Chen Cha, Roy Bhaskar, Li Qun, Zhang Wei, Zhang Xuan, Pu Jieying, Li Yuguang, Liu Yanli, Liao Huanlan, Wang Jingjing, Zhou Rui, Zhuo Huiyan, Li Youqiang
机构信息
Department of Clinical Laboratory, Panyu Hexian Memorial Hospital of Guangzhou, Guangzhou, Guangdong, China.
Department of Clinical Laboratory, The Third People's Hospital of Chengdu, Chengdu, Sichuan, China.
出版信息
Front Oncol. 2025 Feb 27;15:1530677. doi: 10.3389/fonc.2025.1530677. eCollection 2025.
BACKGROUND
Long noncoding RNAs (lncRNAs) HIF1A-AS2 is upregulated in multiple human cancers and are associated with various aspects of tumor progression. However, the molecular mechanisms of HIF1A-AS2 in cervical cancer (CC) remain largely unknown. In this study, we aim to investigate the expression pattern and signaling pathways of HIF1A-AS2 in CC.
METHODS
The study included a group of 20 CC patients, from whom tumor tissue specimens were collected. Additionally, three distinct CC cell lines (HeLa, SiHa, CaSki) were utilized. Quantitative real-time PCR (qRT-PCR) was used to assess the transcript levels of HIF1A-AS2 in these samples. Functional studies were performed by CCK-8, Transwell and Apoptosis assays. Databases including JASPAR, miRDB and Targetscan were used for the transcription factor or target miRNA prediction, subsequent dual luciferase activity assay, chromatin immunoprecipitation (ChIP) and Ago2 immunoprecipitation (RIP) were also adopted for validation.
RESULTS
The study demonstrated that HIF1A-AS2 expression was elevated in clinical cervical cancer specimens and cultured cell lines in comparison to normal controls. Knockdown of HIF1A-AS2 notably inhibited the proliferation and invasion of cervical cancer cells, while inducing apoptosis. In contrast, HIF1A-AS2 overexpression promoted cellular proliferation and invasion and suppressed apoptosis. It was also identified that c-Jun functions as a transcription factor, activating HIF1A-AS2 expression. Additionally, HIF1A-AS2 was found to serve as a molecular sponge for miR-34b-5p, negatively regulating its expression. Furthermore, HIF1A-AS2 controlled the expression of radixin (RDX) by sponging the miR-34b-5p pathway.
CONCLUSION
Our findings indicate that c-Jun-activated HIF1A-AS2 acts as an oncogenic factor in CC by sponging miR-34b-5p to target radixin. These findings suggest that HIF1A-AS2 might be a viable and promising therapeutic target for cervical cancer treatment.
背景
长链非编码RNA（lncRNA）HIF1A-AS2在多种人类癌症中上调，并与肿瘤进展的各个方面相关。然而，HIF1A-AS2在宫颈癌（CC）中的分子机制仍 largely未知。在本研究中，我们旨在研究HIF1A-AS2在CC中的表达模式和信号通路。
方法
该研究纳入了一组20例CC患者，收集了他们的肿瘤组织标本。此外，还使用了三种不同的CC细胞系（HeLa、SiHa、CaSki）。采用定量实时PCR（qRT-PCR）评估这些样本中HIF1A-AS2的转录水平。通过CCK-8、Transwell和凋亡检测进行功能研究。使用包括JASPAR、miRDB和Targetscan在内的数据库进行转录因子或靶miRNA预测，随后还采用双荧光素酶活性检测、染色质免疫沉淀（ChIP）和AGO2免疫沉淀（RIP）进行验证。
结果
研究表明，与正常对照相比，临床宫颈癌标本和培养的细胞系中HIF1A-AS2表达升高。敲低HIF1A-AS2显著抑制宫颈癌细胞的增殖和侵袭，同时诱导凋亡。相反，HIF1A-AS2过表达促进细胞增殖和侵袭并抑制凋亡。还发现c-Jun作为转录因子，激活HIF1A-AS2表达。此外，发现HIF1A-AS2作为miR-34b-5p的分子海绵，负向调节其表达。此外，HIF1A-AS2通过海绵化miR-34b-5p途径控制radixin（RDX）的表达。
结论
我们的研究结果表明，c-Jun激活的HIF1A-AS2通过海绵化miR-34b-
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