Circ_0014130 is involved in the drug sensitivity of colorectal cancer through miR-197-3p/PFKFB3 axis

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Colorectal cancer (CRC) presents a significant global health challenge with limited effective treatments.
• Circular RNAs are increasingly implicated in CRC, yet the specific role of circ_0014130 remains unexplored.
• Understanding novel molecular mechanisms is crucial for advancing CRC therapy.

Purpose of the Study:

• To investigate the functional role of circ_0014130 in colorectal cancer.
• To determine the impact of circ_0014130 on 5-fluorouracil (5-FU) resistance in CRC.
• To elucidate the molecular pathway involving circ_0014130, microRNA-197-3p (miR-197-3p), and 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 3 (PFKFB3).

Main Methods:

• Quantitative real-time polymerase chain reaction (qRT-PCR) to measure nucleic acid expression.
• Western blot analysis for protein expression detection.
• In vitro assays (Cell Counting Kit-8, clone formation, Transwell, flow cytometry) to assess cellular effects.
• In vivo xenograft tumor models to evaluate therapeutic efficacy.

Main Results:

• Circ_0014130 and PFKFB3 expression were elevated, while miR-197-3p was decreased in CRC tissues and cells.
• Knockdown of circ_0014130 inhibited CRC cell proliferation, promoted apoptosis, and decreased 5-FU resistance.
• The miR-197-3p/PFKFB3 axis was identified as the key mediator of circ_0014130's effects on 5-FU resistance.

Conclusions:

• Circ_0014130 significantly influences 5-FU resistance in colorectal cancer.
• The circ_0014130/miR-197-3p/PFKFB3 axis represents a novel therapeutic target for enhancing CRC chemotherapy efficacy.
• Targeting circ_0014130 may offer a promising strategy to overcome drug resistance in CRC patients.