PDGF-BB secreted by OTSCC orchestrates CAF-driven tumor progression through regulating the...

Under the induction of factors derived from tumor cells, fibroblasts can transform into cancer-associated fibroblasts (CAFs), in which non-coding RNAs play a key role. This study aims to reveal the regulatory mechanisms of long non-coding RNAs (lncRNAs) in CAFs induced by PDGF-BB from oral tongue squamous carcinoma cells. This study found that PDGF-BB effectively induces the transformation of fibroblasts into cancer-associated fibroblasts (CAFs). Through focused analysis of transcriptional results, it was discovered that LINC00886 is significantly overexpressed in CAFs (PDGF-BB). Furthermore, knocking down LINC00886 in CAFs (PDGF-BB) resulted in a reversal of related CAF markers, including downregulation of CAF marker proteins, reduced lactate secretion, and inhibition of aerobic glycolysis. Additionally, as a long non-coding RNA, LINC00886 regulates cellular biological behaviors through interactions with miRNAs. Predictions from the ENCORI online database revealed that LINC00886 can interact with hsa-miR-15b-5p. Further analysis indicated that the AKT-mTOR signaling pathway is inhibited in the transcriptome data of CAFs with knocked-down LINC00886. When an inhibitor of hsa-miR-15b-5p was added to CAFs (sh-LINC00886), the total AKT protein level was significantly upregulated, and the phosphorylation level of mTOR was also upregulated. This result was confirmed in a xenograft model. Our study demonstrates that PDGF-BB induces the transformation of fibroblasts into CAFs and thereby promotes tumor progression by regulating the LINC00886/hsa-miR-15b-5p/AKT signaling axis, providing new potential targets for cancer therapy.