Abstract
BackgroundPancreatic cancer (PC) is highly malignant. Chemotherapy is the main treatment strategy, especially for patients with advanced PC. However, chemoresistance has always been a frequently encountered bottleneck. Hence, there is an urgent need to enhance the sensitivity of PC to gemcitabine (GEM).ResultsWe demonstrated that SH3BP5-AS1 was significantly upregulated in GEM-resistant PC and predicted a poorer prognosis. SH3BP5-AS1 stability was regulated by ALKBH5/IGF2BP1-mediated m6A modification. Loss of SH3BP5-AS1 reduced PC cell migration and invasion and enhanced the sensitivity of PC to GEM, as confirmed by gain- and loss-of-function assays in vitro and in vivo. Bioinformatics analysis revealed that SH3BP5-AS1 acted as a ceRNA against miR-139-5p and directly targeted CTBP1, affecting the biological behavior of PC cells. The mechanistic studies revealed that the upregulation of SH3BP5-AS1 increased CTBP1 expression by directly activating the Wnt signaling pathway, promoting GEM resistance.ConclusionsThis study revealed that SH3BP5-AS1 activated Wnt signaling pathway by sponging miR-139-5p, upregulating CTBP1 expression, and contributing to the sensitivity of PC cells to GEM. SH3BP5-AS1 might be a potential target for PC therapy.
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