lncRNA HIF1A-AS2 Acts as an Oncogene to Regulate Malignant Phenotypes in Cervical Cancer

Yang Liu ^1,2 Yunyan Zhang ³ Cha Chen ⁴ Dr.Bhaskar Roy ^5* Qun Li ⁶ Wei Zhang ⁷ Xuan Zhang ⁴ Jieying Pu ⁴ Yu-guang Li ¹ Yanli Liu ¹ Huanlan Liao ⁴ Jingjing Wang ¹ Rui Zhou ¹ Huiyan Zhuo ¹ Youqiang Li ^1*

• ¹ Department of Clinical Laboratory, Panyu Hexian Memorial Hospital of Guangzhou, Qinghe East Road No.2, Guangzhou, Guangdong 511400, China., Guangzhou, China
• ² Department of Clinical Laboratory, The Third People's Hospital of Chengdu, No.82 Qinglong Street, Chengdu, Sichuan 610031, China., Chengdu, China
• ³ Department of pediatric dentistry, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510140, China., Guangzhou, China
• ⁴ Department of laboratory medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, 111 Dade Road, Guangzhou, Guangdong 510006, China., Guangzhou, China
• ⁵ Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China
• ⁶ Department of laboratory medicine, Guangzhou Liwan District people's Hospital, Guangzhou, Guangdong 510006, China., Guangzhou, China
• ⁷ College of Life Sciences, University of Chinese Academy of Sciences, Beijing 101408, China, Beijing, China

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.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 adpoted for validation.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.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.