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<p>Esophageal squamous cell carcinoma (ESCC) ranks as the sixth leading cause of cancer-related deaths globally, with over half of these cases occurring in China. However, the underlying molecular mechanisms of this disease are still not fully elucidated. Numerous circular RNAs (circRNAs) have been implicated in the initiation and progression of malignant tumors through diverse molecular pathways. Nevertheless, the clinical significance and functional roles of the majority of circRNAs associated with ESCC progression remain inadequately characterized. In the present study, we identified a novel circular RNA, designated as circPRKAR1B, which was found to be upregulated in esophageal squamous cell carcinoma (ESCC) tissues and associated with poor prognosis in ESCC patients. Functionally, the overexpression of circPRKAR1B enhanced the proliferation and invasive capabilities of ESCC cells. Mechanistically, circPRKAR1B facilitates the progression of ESCC by interacting with PKM2, which in turn activates the NF-κB signaling pathway, thereby promoting the secretion of CCL3. Additionally, EIF4A3 promotes the expression of circPRKAR1B by binding to its downstream flanking sequences. These findings reveal a previously unrecognized role of circular RNA in the progression of ESCC.</p>

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EIF4A3-induced circPRKAR1B promotes esophageal squamous cell carcinoma progression through binding PKM2 to regulate NF-κB induced CCL3 secretion

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月16日

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  • Shiji Li,
  • Junji Ma,
  • Wenxiu Jia,
  • Yangyang Duan,
  • Jingran Wang,
  • Xiuning Zhang,
  • Yan Han

摘要

Esophageal squamous cell carcinoma (ESCC) ranks as the sixth leading cause of cancer-related deaths globally, with over half of these cases occurring in China. However, the underlying molecular mechanisms of this disease are still not fully elucidated. Numerous circular RNAs (circRNAs) have been implicated in the initiation and progression of malignant tumors through diverse molecular pathways. Nevertheless, the clinical significance and functional roles of the majority of circRNAs associated with ESCC progression remain inadequately characterized. In the present study, we identified a novel circular RNA, designated as circPRKAR1B, which was found to be upregulated in esophageal squamous cell carcinoma (ESCC) tissues and associated with poor prognosis in ESCC patients. Functionally, the overexpression of circPRKAR1B enhanced the proliferation and invasive capabilities of ESCC cells. Mechanistically, circPRKAR1B facilitates the progression of ESCC by interacting with PKM2, which in turn activates the NF-κB signaling pathway, thereby promoting the secretion of CCL3. Additionally, EIF4A3 promotes the expression of circPRKAR1B by binding to its downstream flanking sequences. These findings reveal a previously unrecognized role of circular RNA in the progression of ESCC.