circ5615 functions as a ceRNA to promote colorectal cancer progression by upregulating TNKS

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Circular RNAs (circRNAs) are increasingly recognized for their roles in various cancers.
• The specific functions of many circRNAs in colorectal cancer (CRC) remain largely unexplored.
• Understanding novel circRNAs in CRC is crucial for identifying new diagnostic and therapeutic strategies.

Purpose of the Study:

• To investigate the expression and function of circRNAs in colorectal cancer (CRC).
• To identify specific circRNAs involved in CRC progression and their underlying molecular mechanisms.
• To explore the potential of circRNAs as biomarkers or therapeutic targets in CRC.

Main Methods:

• Microarray analysis of circRNA expression in paired CRC and normal tissues.
• In vitro and in vivo experiments to assess the functional role of hsa_circ_0005615 (circ5615) in cancer cells.
• RNA immunoprecipitation, pull-down assays, and luciferase reporter assays to elucidate molecular interactions.
• RNA sequencing and bioinformatics analysis to identify downstream targets and pathways.

Main Results:

• hsa_circ_0005615 (circ5615) was significantly upregulated in CRC tissues and correlated with advanced T stage and poor prognosis.
• Knockdown of circ5615 inhibited CRC cell proliferation and cell cycle progression, while overexpression promoted malignant phenotypes.
• circ5615 acts as a molecular sponge for miR-149-5p, releasing its target tankyrase (TNKS).
• circ5615 upregulates downstream targets β-catenin and cyclin D1, activating the Wnt/β-catenin pathway.

Conclusions:

• circ5615 functions as an oncogenic circular RNA in colorectal cancer.
• It operates via a competing endogenous RNA (ceRNA) mechanism, sponging miR-149-5p to regulate TNKS and activate the Wnt/β-catenin pathway.
• circ5615 represents a potential diagnostic biomarker and therapeutic target for colorectal cancer.