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Long noncoding RNA SNHG5 promotes 5-fluorouracil resistance in colorectal cancer by regulating miR-26b/p-glycoprotein
Bin Wang1,2, Qian Zhou2, Cui-E Cheng2
1School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China.
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 SNHG5 is highly expressed in CRC and promotes tumor proliferation and invasion, prompting us to hypothesize that SNHG5 may play a crucial role in the chemotherapeutic agent 5-fluorouracil (5-Fu) resistance in CRC.
Aim:
To identify the function and mechanism of SNHG5 in 5-Fu resistance in CRC.
Methods:
Quantitative real-time polymerase chain reaction was performed to examine the expression of SNHG5 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 SNHG5-overexpressing CRC cells and SNHG5-knockdown 5-Fu-resistant CRC cells. SNHG5 function in 5-Fu resistance in CRC was further analyzed using a xenograft mouse model. SNHG5 interactions with microRNAs were predicted by bioinformatics analysis. Luciferase reporter and RNA immunoprecipitation assays were performed to verify the binding between SNHG5 and miR-26b. Rescue experiments were performed to validate the functional interaction between SNHG5 and the miR-26b/p-glycoprotein (Pgp) axis.
Results:
SNHG5 expression was upregulated in 5-Fu-resistant CRC tissues and 5-Fu-resistant CRC cells. In vitro functional experiments demonstrated that SNHG5 overexpression significantly reduced cell apoptosis and enhanced cell viability, whereas SNHG5 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 SNHG5 overexpression led to a reduction in 5-Fu sensitivity in CRC in vivo. Mechanistically, SNHG5 acted as a molecular sponge for miR-26b. Rescue experiments validated that SNHG5 conferred 5-Fu resistance in CRC by regulating the miR-26b/Pgp axis.
Conclusion:
SNHG5/miR-26b/Pgp regulates CRC chemosensitivity, providing potential therapeutic targets for the treatment of 5-Fu-resistant CRC.
