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Zeng et al. Cancer Drug Resist 2024;7:31 https://dx.doi.org/10.20517/cdr.2024.57 Page 7 of 13

Figure 1. circRNAs are closely associated with signaling pathways involved in drug resistance of HNSCC. circRNAs: Circular RNAs;
HNSCC: head and neck squamous cell carcinoma.

functions as a sponge of miR-515-5p, leading to miR-515-5p inhibition and interleukin 25 (IL-25)
upregulation. This mechanism promotes chemotherapy resistance in NPC by enhancing the expression of
[93]
IL-25, which can be directly targeted by miR-515-5p . circSETD3 is upregulated in NPC and is related to
cisplatin resistance in this carcinoma. Knockdown of circSETD3 can inhibit NPC proliferation, enhance
cisplatin sensitivity, and increase the apoptosis rate. circSETD3, a sponge for miR-147a, promotes activation
of the AKT/mTOR pathway. circSETD3 promotes NPC proliferation and cisplatin resistance by
manipulating miR-147a .
[34]

circRNAs and chemoresistance of laryngeal squamous cell carcinoma
circRNAs affect the chemotherapy resistance of LSCC. For example, circPGM1 interacts with miR-376a as a
ceRNA to regulate the drug resistance of LSCC. The autophagy-related protein 2A (ATG2A) is a key
effector of circPGAM1/miR-376a axis-mediated resistance. Overexpression of ATG2A significantly inhibits
miR-376a on cisplatin resistance in LSCC. circPGAM1 functions as a miR-376a sponge, promoting the
[94]
expression of ATG2A and subsequently enhancing autophagy, leading to cisplatin resistance in LSCC .
Gao et al. observed a significant association between elevated circPARD3 expression and tumor stages and
cervical lymph node metastasis of LSCC patients . Moreover, high circPARD3 caused significantly shorter
[68]
overall survival of LSCC patients. circPARD3 functions as a miRNA-145-5p sponge, upregulating the
expression of protein kinase C iota (PRKCI) and further activating the AKT/mTOR signaling axis,
promoting the proliferation, migration, invasion and chemotherapy resistance of LSCC . Yi et al. observed
[68]
elevated expression of circ-0004507 in LSCC and noted a positive correlation between its expression and
tumor stage, differentiation degree, and lymph node metastasis rate . circ-0004507 was highly expressed in
[95]
the cancer tissues of chemotherapy-resistant patients. Through its role as a miR-873 sponge, circ-0004507
downregulates the expression of miR-873, thereby reducing the sensitivity of laryngeal cancer to cisplatin
chemotherapy . Additionally, Gong et al. showed that circ-0005033 was highly expressed in laryngeal
[95]
cancer tissues, compared with normal laryngeal epithelial tissues, and circ-0005033 functions as a ceRNA
for miR-107 in LSCC . High expression of circ-0005033 downregulates miRNA-107 expression, promoting
[70]
insulin-like growth factor-1 receptor (IGF1R) expression and subsequently enhancing the proliferation,
invasion, migration, and cisplatin resistance of LSCC .
[70]