Long noncoding RNA promotes 5-fluorouracil resistance in colorectal cancer by regulating miR-26b/p-glycoprotein axis.

Background: Colorectal cancer (CRC) is the second most prevalent cause of cancer-related mortality and is increasing in younger individuals. Chemotherapy, a crucial adjuvant systemic therapy for CRC management, often leads to resistance through poorly characterized underlying molecular mechanisms. The long noncoding RNA is highly expressed in CRC and promotes tumor proliferation and invasion, prompting us to hypothesize that may play a crucial role in the chemotherapeutic agent 5-fluorouracil (5-Fu) resistance in CRC.

Aim: To identify the function and mechanism of in 5-Fu resistance in CRC.

Methods: Quantitative real-time polymerase chain reaction was performed to examine the expression of in CRC tissues from 22 5-Fu-sensitive patients and 14 5-Fu-resistant patients and in CRC cells and 5-Fu-resistant CRC cells. Cell viability and apoptosis were assessed in -overexpressing CRC cells and -knockdown 5-Fu-resistant CRC cells. function in 5-Fu resistance in CRC was further analyzed using a xenograft mouse model. interactions with microRNAs were predicted by bioinformatics analysis. Luciferase reporter and RNA immunoprecipitation assays were performed to verify the binding between and miR-26b. Rescue experiments were performed to validate the functional interaction between and the miR-26b/p-glycoprotein (Pgp) axis.

Results: expression was upregulated in 5-Fu-resistant CRC tissues and 5-Fu-resistant CRC cells. functional experiments demonstrated that overexpression significantly reduced cell apoptosis and enhanced cell viability, whereas knockdown in 5-Fu-resistant CRC cells increased cell apoptosis and decreased cell viability upon 5-Fu treatment. In a xenograft mouse model, we confirmed that overexpression led to a reduction in 5-Fu sensitivity in CRC . Mechanistically, acted as a molecular sponge for miR-26b. Rescue experiments validated that conferred 5-Fu resistance in CRC by regulating the miR-26b/Pgp axis.

Conclusion: /miR-26b/Pgp regulates CRC chemosensitivity, providing potential therapeutic targets for the treatment of 5-Fu-resistant CRC.