Circ‐ILF2 in oral squamous cell carcinoma promotes cisplatin resistance and induces M2 polarization of macrophages

Abstract

Cisplatin (CDDP) chemoresistance is one of the predominant factors in oral squamous cell carcinoma (OSCC) treatment failure. Uncovering the mechanisms underlying CDDP resistance is of great importance in OSCC therapy. Circular RNAs (circRNAs) are a newly discovered class of noncoding RNAs, which are reported to participate in the progression of various diseases, including cancer. However, the function of circRNAs in CDDP resistance in OSCC remains unclear. Quantitative reverse transcription PCR was used to search for different circRNAs between OSCC cell lines and CDDP‐resistant cell lines. The results showed that circ‐ILF2 expression was higher in CDDP‐resistant OSCC cell lines. The stability of circ‐ILF2 was also confirmed using RNase R and actinomycin D assays. Functional experiments, including cytotoxicity, apoptosis and growth rate assays, showed that upregulation of circ‐ILF2 contributes to CDDP resistance. Luciferase reporter‐gene, RNA pull‐down and quantitative real‐time PCR (RT‐qPCR) assays showed that circ‐ILF2 functions as a microRNA sponge for miR‐1252. Luciferase reporter assays, RNA pull‐down, RT‐qPCR and Western blotting showed that miR‐1252 directly targeted and regulated the expression of KLF8. Circ‐ILF2 plays an important role in CDDP resistance in OSCC. Circ‐ILF2 exerts its function through the miR‐1252/KLF8 pathway. In addition, tumour‐associated macrophages (TAM) play important roles in cancer progressions, our results showed that circ‐ILF2 in OSCC cells induced the M2 polarization of macrophages which provided new thoughts on immunotherapy. Our results suggest that circ‐ILF2 may represent a potential therapeutic target in CDDP‐resistant OSCC.

The novel circ_0004674/miR‐139‐5p/ZBTB2 regulatory cascade inhibits the development of oral squamous cell carcinoma

“…Moreover, circ_0069313 contributes to OSCC immunity escape to induce this disease progression by targeting miR‐325‐3p/Foxp3 axis 24 . Circ‐ILF2 causes M2 macrophage polarization to enhance cancer cell resistance to cisplatin 25 . Conversely, circ_0000140 has been reported to function as a suppressor in OSCC by regulating miR‐31 26 .…”

“…24 Circ-ILF2 causes M2 macrophage polarization to enhance cancer cell resistance to cisplatin. 25 Conversely, circ_0000140 has been reported to function as a suppressor in OSCC by regulating miR-31. 26 Here, we confirm the significant up-regulation of circ_0004674 in OSCC.…”

Targeting ferroptosis as a potential strategy to overcome the resistance of cisplatin in oral squamous cell carcinoma

“…Circ-ILF2 serves as a sponge of miR-1252, downregulating the level of Krüppel-like factor 8 ( KLF8 ) in OSCC cells. The upregulation of circ-ILF2 can greatly decrease cisplatin-induced apoptosis and induce the M2 polarization of macrophages through circ-ILF2/miR-1252 / KLF8 axis ( Wu et al, 2023b ).…”