Circular RNAs (circRNAs) has been shown to play an important role in the progression of various cancers. However, the function and underlying mechanisms of circRNAs affecting chemotherapy resistance in esophageal squamous cell carcinoma (ESCC) remain largely unknown. In this study, we used gefitinib‐resistant (GR) ESCC cells to investigate the function of circPSMC3 and clarify the underlying mechanism in chemotherapy resistance in ESCC. The results suggested that circPSMC3 expression was downregulated, but miR‐10a‐5p was upregulated in ESCC tissues and cells, as well as in GR ESCC cells. CircPSMC3 overexpression increased the sensitivity of ESCC cells to gefitinib, as indicated by reduced half maximal inhibitory concentration value, increased apoptosis rate and cleaved caspase‐3 protein expression. CircPSMC3 directly interacted with miR‐10a‐5p and inhibited the expression of miR‐10a‐5p. Phosphatase and tensin homolog (PTEN) was a direct target of miR‐10a‐5p and circPSMC3 promoted PTEN expression via decreasing miR‐10a‐5p level. Moreover, the effect of circPSMC3 on resistance of GR ESCC cells to gefitinib was remarkably reduced by restoration of miR‐10a‐5p and downregultion of PTEN. Taken together, these observations suggested that upregulation of circPSMC3 overcame resistance of GR ESCC cells to gefitinib by modulating the miR‐10a‐5p/PTEN axis, which provide a new therapeutic strategy for overcoming gefitinib resistance in ESCC.

中文翻译：

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circPSMC3的恢复通过调节miR-10a-5p/PTEN轴使吉非替尼耐药的食管鳞状细胞癌细胞对吉非替尼敏感

环状RNA（circRNA）已被证明在各种癌症的进展中发挥着重要作用。然而，影响食管鳞状细胞癌（ESCC）化疗耐药性的circRNA的功能和潜在机制仍然未知。在这项研究中，我们使用吉非替尼耐药 (GR) ESCC 细胞来研究 circPSMC3 的功能，并阐明 ESCC 化疗耐药的潜在机制。结果表明 circPSMC3 表达下调，但 miR-10a-5p 在 ESCC 组织和细胞以及 GR ESCC 细胞中上调。CircPSMC3 过表达增加了 ESCC 细胞对吉非替尼的敏感性，这表现为半数抑制浓度值降低、细胞凋亡率增加和 caspase-3 蛋白表达裂解。CircPSMC3 直接与 miR-10a-5p 相互作用并抑制 miR-10a-5p 的表达。磷酸酶和张力蛋白同源物（PTEN）是 miR-10a-5p 的直接靶标，circPSMC3 通过降低 miR-10a-5p 水平促进 PTEN 表达。此外，通过miR-10a-5p的恢复和PTEN的下调，circPSMC3对GR ESCC细胞对吉非替尼耐药的影响显着降低。综上所述，这些观察结果表明，circPSMC3 的上调通过调节 miR-10a-5p/PTEN 轴克服了 GR ESCC 细胞对吉非替尼的耐药性，这为克服 ESCC 中的吉非替尼耐药性提供了一种新的治疗策略。通过miR-10a-5p的恢复和PTEN的下调，circPSMC3对GR ESCC细胞对吉非替尼耐药的影响显着降低。综上所述，这些观察结果表明，circPSMC3 的上调通过调节 miR-10a-5p/PTEN 轴克服了 GR ESCC 细胞对吉非替尼的耐药性，这为克服 ESCC 中的吉非替尼耐药性提供了一种新的治疗策略。通过miR-10a-5p的恢复和PTEN的下调，circPSMC3对GR ESCC细胞对吉非替尼耐药的影响显着降低。综上所述，这些观察结果表明，circPSMC3 的上调通过调节 miR-10a-5p/PTEN 轴克服了 GR ESCC 细胞对吉非替尼的耐药性，这为克服 ESCC 中的吉非替尼耐药性提供了一种新的治疗策略。