What question did this study set out to answer?

The study aims to explore circCDK6's role in cancer stem cell maintenance and cisplatin resistance in lung adenocarcinoma through the Wnt/β-catenin pathway.

May 17, 2026Open Access

CircCDK6 Regulates Stemness Maintenance and Cisplatin Resistance in Lung Adenocarcinoma via the Wnt/β-Catenin Signaling Pathway

DLDan LiJiangnan University YSYanwei ShenShanxi Medical University LWLi WangCentral South University

Key Points

The study aims to explore circCDK6's role in cancer stem cell maintenance and cisplatin resistance in lung adenocarcinoma through the Wnt/β-catenin pathway.
Measured circCDK6 levels using quantitative real-time PCR in various LUAD cell lines.
Conducted gain- and loss-of-function experiments via plasmid overexpression and siRNA knockdown of circCDK6.
Assessed cisplatin sensitivity using Cell Counting Kit-8 and colony formation assays, and used IWR-1 to inhibit the Wnt/β-catenin pathway.
CircCDK6 expression was higher in H1299 and H1975 cells than in A549 and PC-9 cells.
Overexpression of circCDK6 increased stemness markers (CD133, Oct4, Sox2) and enhanced cisplatin resistance, as shown by elevated IC50 values.
Knockdown of circCDK6 significantly reduced tumor volume and improved cisplatin efficacy, linked with decreased Ki-67 expression.

Abstract

Objective: This study investigates the role of circCDK6 in maintaining cancer stem cell (CSC) properties and mediating cisplatin resistance in lung adenocarcinoma (LUAD), with a focus on the involvement of the Wnt/β-catenin signaling pathway. Methods: The expression levels of circCDK6 in various LUAD cell lines were measured using quantitative real-time PCR. Gain- and loss-of-function experiments were conducted by plasmid-mediated overexpression and siRNA-mediated knockdown of circCDK6. Cisplatin sensitivity was assessed using the Cell Counting Kit-8 assay and colony formation assay. The involvement of the Wnt/β-catenin pathway was examined by inhibiting the pathway with IWR-1. A subcutaneous xenograft model in BALB/c nude mice was used to evaluate the in vivo effects of circCDK6 knockdown on cisplatin responsiveness, and tumor tissues were analyzed through hematoxylin and eosin staining and immunohistochemistry for Ki-67 expression. Results: CircCDK6 expression was significantly elevated in H1299 and H1975 cells compared to A549 and PC-9 cells. Overexpression of circCDK6 increased stemness markers, such as CD133, Oct4, and Sox2, and enhanced cisplatin resistance, as demonstrated by higher IC 50 values and increased colony formation. In contrast, circCDK6 silencing significantly reduced cisplatin resistance. Western blot analysis revealed that circCDK6 activated the Wnt/β-catenin pathway by upregulating Axin2, β-catenin, and c-Myc. In vivo, circCDK6 knockdown reduced tumor volume, improved the anti-tumor effect of cisplatin, and decreased Ki-67 expression. Conclusion: CircCDK6 may promote CSC properties and contribute to cisplatin resistance in LUAD, potentially through activation of the Wnt/β-catenin pathway. These findings suggest that circCDK6 may represent a potential therapeutic target for overcoming chemoresistance in LUAD, although further studies are needed to validate its role and clinical relevance. Keywords: cancer stem cell-like properties, chemoresistance mechanisms, noncoding RNA, lung cancer progression, β-catenin signaling

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