Comprehensive Analysis of circRNA Expression Profiles During Cervical Carcinogenesis

Area of Science:

• Oncology
• Molecular Biology
• Genomics

Background:

• Circular RNAs (circRNAs) are crucial regulatory molecules in tumor occurrence, development, and progression.
• Understanding the temporal transcriptomic changes in cervical carcinogenesis is essential for identifying key molecular events.

Purpose of the Study:

• To analyze the temporal transcriptomic landscapes of mRNAs and circRNAs during cervical carcinogenesis.
• To identify functional circRNAs and mRNAs associated with cervical squamous cell carcinoma (CSCC) and high-grade squamous intraepithelial lesion (HSIL).

Main Methods:

• Microarray analysis to profile circRNA and mRNA expression in normal controls (NC), HSIL, and CSCC.
• Short time-series expression miner (STEM) to identify time-course expression patterns.
• Protein-protein interaction (PPI) network and competing endogenous RNA (ceRNA) network analyses.
• Real-time PCR validation and in vitro functional assays (cell proliferation, cell cycle).

Main Results:

• Identified 3 circRNA and 3 mRNA profiles with continuous upregulation from NC to CSCC.
• Functional annotation linked mRNAs to DNA repair and cell division.
• Discovered key circRNA-miRNA-mRNA axes (e.g., hsa_circ_0003954/hsa-miR-15a-3p/SYCP2) correlated with cervical carcinogenesis.
• Silencing hsa_circ_0003954 inhibited SiHa cell proliferation and perturbed the cell cycle.

Conclusions:

• This study provides a comprehensive blueprint of cervical carcinogenesis at the transcriptomic level.
• Identified functional circRNAs (e.g., hsa_circ_0003954) as potential drivers and biomarkers for CSCC and HSIL.
• Enhances understanding of the pathogenesis and molecular mechanisms underlying cervical cancer development.