Department of Clinical Laboratory, Huaihe Hospital of Henan University, Kaifeng, Henan, China.
Department of Hematology and Oncology, No. 988 Hospital of Joint Logistic Support Force of the Chinese People's Liberation Army, Zhengzhou, Henan, China.
Cell Biol Int. 2021 Jan;45(1):107-116. doi: 10.1002/cbin.11473. Epub 2020 Oct 12.
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.
环状 RNA（circRNAs）已被证明在多种癌症的进展中发挥重要作用。然而，circRNAs 影响食管鳞状细胞癌（ESCC）化疗耐药的功能和潜在机制在很大程度上仍不清楚。在本研究中，我们使用吉非替尼耐药（GR）ESCC 细胞来研究 circPSMC3 的功能，并阐明其在 ESCC 化疗耐药中的潜在机制。结果表明，circPSMC3 在 ESCC 组织和细胞以及 GR ESCC 细胞中表达下调，而 miR-10a-5p 表达上调。circPSMC3 的过表达降低了 ESCC 细胞对吉非替尼的半数抑制浓度值，增加了细胞凋亡率和 cleaved caspase-3 蛋白表达，从而提高了 ESCC 细胞对吉非替尼的敏感性。circPSMC3 可以直接与 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，miR-10a-5p 和 PTEN 的恢复以及 circPSMC3 的下调显著降低了 circPSMC3 对 GR ESCC 细胞对吉非替尼耐药的影响。综上所述，这些结果表明，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，为克服 ESCC 对吉非替尼的耐药性提供了一种新的治疗策略。
