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

IF 5.3 2区医学 Q1 ONCOLOGY

Cancer Cell International Pub Date : 2025-07-16 DOI:10.1186/s12935-025-03905-9

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

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Abstract

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.

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eif4a3诱导的circPRKAR1B通过结合PKM2调控NF-κB诱导的CCL3分泌，促进食管鳞状细胞癌的进展。

食管鳞状细胞癌（ESCC）是全球第六大癌症相关死亡原因，其中超过一半的病例发生在中国。然而，这种疾病的潜在分子机制仍未完全阐明。许多环状rna （circRNAs）通过不同的分子途径参与恶性肿瘤的发生和发展。然而，大多数与ESCC进展相关的circrna的临床意义和功能作用仍然没有得到充分的描述。在本研究中，我们发现了一种新的环状RNA，命名为circPRKAR1B，该环状RNA在食管鳞状细胞癌（ESCC）组织中表达上调，并与ESCC患者预后不良相关。在功能上，circPRKAR1B的过表达增强了ESCC细胞的增殖和侵袭能力。从机制上讲，circPRKAR1B通过与PKM2相互作用促进ESCC的进展，进而激活NF-κB信号通路，从而促进CCL3的分泌。此外，EIF4A3通过结合circPRKAR1B的下游侧翼序列促进circPRKAR1B的表达。这些发现揭示了环状RNA在ESCC进展中以前未被认识到的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Cell International ONCOLOGY-

CiteScore

10.90

自引率

1.70%

发文量

360

审稿时长

1 months

期刊介绍： Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.