hsa_circ_0135681 functions as a novel tumor-suppressive circular RNA regulating Glycolysis and EMT to attenuate cisplatin resistance in non-small cell lung cancer.
[BACKGROUND] Circular RNAs (circRNAs) play critical roles in tumorigenesis.
APA
Song X, Li H, et al. (2025). hsa_circ_0135681 functions as a novel tumor-suppressive circular RNA regulating Glycolysis and EMT to attenuate cisplatin resistance in non-small cell lung cancer.. Discover oncology, 17(1), 3. https://doi.org/10.1007/s12672-025-04024-7
MLA
Song X, et al.. "hsa_circ_0135681 functions as a novel tumor-suppressive circular RNA regulating Glycolysis and EMT to attenuate cisplatin resistance in non-small cell lung cancer.." Discover oncology, vol. 17, no. 1, 2025, pp. 3.
PMID
41307824
Abstract
[BACKGROUND] Circular RNAs (circRNAs) play critical roles in tumorigenesis. However, their function in cisplatin (CDDP) resistance of non-small cell lung cancer (NSCLC) remains incompletely understood. We aimed to investigate the expression pattern of hsa_circ_0135681 in NSCLC and its role in regulating cisplatin resistance.
[METHOD] RNA sequencing was performed on serum samples to identify differentially expressed circRNAs (DEcircRNAs) using thresholds of |log2FC| >1 and < 0.05. We validated candidate DEcircRNAs via quantitative real-time PCR (qRT-PCR) in NSCLC tissues. We conducted functional assays, including CCK-8 proliferation, wound healing assay, and flow cytometry apoptosis analysis. Finally, nude mouse xenograft models were used to investigate the role of circRNA in . In mechanistic investigations, lactate and glucose detection kits were used, with subsequent validation conducted via Western blot (WB) and qRT-PCR.
[RESULTS] A total of 411 DEcircRNAs were identified in serum samples, and the 9 selected candidate DEcircRNAs were further validated in NSCLC tissues. Among these, hsa_circ_0135681 was significantly downregulated in NSCLC tissues compared to adjacent non-cancerous tissues. Overexpression of hsa_circ_0135681 could inhibit the proliferation and migration of A549/DDP cells, induce apoptosis in , and similarly suppress tumorigenesis in . Mechanistically, hsa_circ_0135681 overexpression reduced glycolytic activity and reversed EMT in A549/DDP cells. Additionally, bioinformatics analysis predicted two potential regulatory axes: hsa_circ_0135681/hsa-miR-4299/RNF180 and hsa_circ_0135681/hsa-miR-4299/SOCS5.
[CONCLUSION] Collectively, hsa_circ_0135681 is a tumor-suppressive circRNA that modulates glycolysis and EMT. These findings may provide a potential therapeutic target for cisplatin-resistant NSCLC.
[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1007/s12672-025-04024-7.
[METHOD] RNA sequencing was performed on serum samples to identify differentially expressed circRNAs (DEcircRNAs) using thresholds of |log2FC| >1 and < 0.05. We validated candidate DEcircRNAs via quantitative real-time PCR (qRT-PCR) in NSCLC tissues. We conducted functional assays, including CCK-8 proliferation, wound healing assay, and flow cytometry apoptosis analysis. Finally, nude mouse xenograft models were used to investigate the role of circRNA in . In mechanistic investigations, lactate and glucose detection kits were used, with subsequent validation conducted via Western blot (WB) and qRT-PCR.
[RESULTS] A total of 411 DEcircRNAs were identified in serum samples, and the 9 selected candidate DEcircRNAs were further validated in NSCLC tissues. Among these, hsa_circ_0135681 was significantly downregulated in NSCLC tissues compared to adjacent non-cancerous tissues. Overexpression of hsa_circ_0135681 could inhibit the proliferation and migration of A549/DDP cells, induce apoptosis in , and similarly suppress tumorigenesis in . Mechanistically, hsa_circ_0135681 overexpression reduced glycolytic activity and reversed EMT in A549/DDP cells. Additionally, bioinformatics analysis predicted two potential regulatory axes: hsa_circ_0135681/hsa-miR-4299/RNF180 and hsa_circ_0135681/hsa-miR-4299/SOCS5.
[CONCLUSION] Collectively, hsa_circ_0135681 is a tumor-suppressive circRNA that modulates glycolysis and EMT. These findings may provide a potential therapeutic target for cisplatin-resistant NSCLC.
[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1007/s12672-025-04024-7.
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