Table 1_lncRNA HIF1A-AS2 acts as an oncogene to regulate malignant phenotypes in cervical cancer.docx

BackgroundLong 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.
MethodsThe 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.
ResultsThe 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.
ConclusionOur 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.

研究背景：长链非编码RNA（long noncoding RNAs，lncRNAs）HIF1A-AS2在多种人类癌症中呈高表达状态，且与肿瘤进展的多个维度密切相关。然而，HIF1A-AS2在宫颈癌（cervical cancer，CC）中的分子调控机制仍有待进一步阐明。本研究旨在探讨HIF1A-AS2在宫颈癌中的表达模式及相关信号通路。
研究方法：本研究纳入20例宫颈癌患者，收集其肿瘤组织标本；同时选用3株不同的宫颈癌细胞系（HeLa、SiHa、CaSki）开展实验。采用实时荧光定量PCR（quantitative real-time PCR，qRT-PCR）检测上述样本中HIF1A-AS2的转录水平。通过CCK-8实验、Transwell实验及细胞凋亡实验进行功能学研究。借助JASPAR、miRDB及Targetscan数据库预测潜在的转录因子或靶miRNA，并通过双荧光素酶活性实验、染色质免疫共沉淀（chromatin immunoprecipitation，ChIP）及Ago2免疫沉淀（RNA immunoprecipitation，RIP）实验对预测结果进行验证。
研究结果：本研究结果显示，与正常对照样本相比，HIF1A-AS2在临床宫颈癌标本及体外培养的宫颈癌细胞系中表达显著上调。敲低HIF1A-AS2可显著抑制宫颈癌细胞的增殖与侵袭能力，并诱导细胞凋亡；反之，过表达HIF1A-AS2则能够促进细胞增殖与侵袭，同时抑制细胞凋亡。研究还证实，c-Jun作为转录因子可激活HIF1A-AS2的表达。此外，HIF1A-AS2可作为miR-34b-5p的分子海绵，负向调控其表达水平。进一步研究发现，HIF1A-AS2通过海绵吸附miR-34b-5p通路调控根蛋白（radixin，RDX）的表达。
研究结论：本研究结果表明，经c-Jun激活的HIF1A-AS2通过海绵吸附miR-34b-5p靶向调控根蛋白，在宫颈癌中发挥致癌因子的作用。上述研究结果提示，HIF1A-AS2有望成为宫颈癌治疗的潜在且极具应用前景的治疗靶点。