CircUCP2 Promotes the Tumor Progression of Non-small Cell Lung Cancer Through the MiR-149/UCP2 Pathway

Overview

Journal Oncol Res

Specialty Oncology

Date 2023 Sep 25

PMID 37744277

Authors

Wei Du

Fang Yin

Yating Zhong

Minjie Luo

Zhen Wang

Peng Lin

Qing Liu

Han Yang

Affiliations

Soon will be listed here.

Abstract

Non-small cell lung cancer (NSCLC) is a highly lethal cancer, and better treatments are urgently needed. Many studies have implicated circular RNAs (circRNAs) in the progression of multiple malignant tumors. Nonetheless, the functions of circRNAs in NSCLC remain unclear. To study new targets for the treatment of NSCLC, circRNA expression profiling was performed on NSCLC tissues and para-carcinoma nonmalignant tissues. RNA was isolated and used for circRNA sequencing. Biological studies were performed and to determine the functions of circRNAs in NSCLC, including their functions in cell proliferation and migration. How circRNAs function in NSCLC was explored to clarify the underlying regulatory mechanisms. We found that circUCP2 was upregulated in NSCLC tissues compared with neighboring nonmalignant tissues. circUCP2 promoted the proliferation and metastasis of NSCLC cells. circUCP2 promoted NSCLC progression by sponging miR-149 and upregulating UCP2. The circUCP2/miR-149/UCP2 axis accelerates the progression of NSCLC, and circUCP2 may therefore be a novel diagnostic biomarker for the progression of NSCLC.

Citing Articles

CircRNA circ_0015278 induces ferroptosis in lung adenocarcinoma through the miR-1228/P53 axis.

Xia L, Li G, Zhou Q, Feng Y, Ma H Oncol Res. 2025; 33(2):465-475.

PMID: 39866239 PMC: 11753987. DOI: 10.32604/or.2024.050835.

Circular RNA circAGAP1 promotes sunitinib sensitivity in renal cell carcinoma via sponging multiple PDGFR-targeted miRNAs.

Lv Q, Wang G, Hong Y, Zhu T, Qin S, Sun S Oncol Res. 2025; 33(2):407-420.

PMID: 39866227 PMC: 11754003. DOI: 10.32604/or.2024.047698.

Proliferation Inhibited by Genipin in Human Leukemia K562 Cells: Involvement of Uncoupling Protein 2 in Mitochondrial Damage.

Zhou Y, Sun R, Zhang Z, He X, Li L, Zhang C World J Oncol. 2025; 16(1):83-94.

PMID: 39850526 PMC: 11750759. DOI: 10.14740/wjon1975.

Mitochondrial uncoupling protein 2: a central player in pancreatic disease pathophysiology.

Wang K, Zhang L, Deng B, Zhao K, Chen C, Wang W Mol Med. 2024; 30(1):259.

PMID: 39707176 PMC: 11660649. DOI: 10.1186/s10020-024-01027-y.

The Role of circHIPK3 in Tumorigenesis and Its Potential as a Biomarker in Lung Cancer.

Siedlecki E, Remiszewski P, Stec R Cells. 2024; 13(17.

PMID: 39273053 PMC: 11393915. DOI: 10.3390/cells13171483.

References

Dando I, Fiorini C, Dalla Pozza E, Padroni C, Costanzo C, Palmieri M . UCP2 inhibition triggers ROS-dependent nuclear translocation of GAPDH and autophagic cell death in pancreatic adenocarcinoma cells. Biochim Biophys Acta. 2012; 1833(3):672-9. DOI: 10.1016/j.bbamcr.2012.10.028. View

Zhou Z, Zhang S, Xiong Y . Long noncoding RNA MIAT promotes non-small cell lung cancer progression by sponging miR-149-5p and regulating FOXM1 expression. Cancer Cell Int. 2020; 20:348. PMC: 7389523. DOI: 10.1186/s12935-020-01432-3. View

Li B, Zhu L, Lu C, Wang C, Wang H, Jin H . circNDUFB2 inhibits non-small cell lung cancer progression via destabilizing IGF2BPs and activating anti-tumor immunity. Nat Commun. 2021; 12(1):295. PMC: 7804955. DOI: 10.1038/s41467-020-20527-z. View

Ma Z, Han C, Xia W, Wang S, Li X, Fang P . circ5615 functions as a ceRNA to promote colorectal cancer progression by upregulating TNKS. Cell Death Dis. 2020; 11(5):356. PMC: 7214456. DOI: 10.1038/s41419-020-2514-0. View

Sanchez-Gonzalez I, Bobien A, Molnar C, Schmid S, Strotbek M, Boerries M . miR-149 Suppresses Breast Cancer Metastasis by Blocking Paracrine Interactions with Macrophages. Cancer Res. 2020; 80(6):1330-1341. DOI: 10.1158/0008-5472.CAN-19-1934. View

Hong M, Choi Y, Jang J, Jung H, Lee S, Lee W . Association between genetic variants in pre-microRNAs and survival of early-stage NSCLC. J Thorac Oncol. 2013; 8(6):703-10. DOI: 10.1097/JTO.0b013e318288dc0a. View

Vo J, Cieslik M, Zhang Y, Shukla S, Xiao L, Zhang Y . The Landscape of Circular RNA in Cancer. Cell. 2019; 176(4):869-881.e13. PMC: 6601354. DOI: 10.1016/j.cell.2018.12.021. View

Li P, Shan J, Chen X, Zhang D, Su L, Huang X . Epigenetic silencing of microRNA-149 in cancer-associated fibroblasts mediates prostaglandin E2/interleukin-6 signaling in the tumor microenvironment. Cell Res. 2015; 25(5):588-603. PMC: 4423088. DOI: 10.1038/cr.2015.51. View

Chen L, Nan A, Zhang N, Jia Y, Li X, Ling Y . Circular RNA 100146 functions as an oncogene through direct binding to miR-361-3p and miR-615-5p in non-small cell lung cancer. Mol Cancer. 2019; 18(1):13. PMC: 6340182. DOI: 10.1186/s12943-019-0943-0. View

10.

Wang L, Tong X, Zhou Z, Wang S, Lei Z, Zhang T . Circular RNA hsa_circ_0008305 (circPTK2) inhibits TGF-β-induced epithelial-mesenchymal transition and metastasis by controlling TIF1γ in non-small cell lung cancer. Mol Cancer. 2018; 17(1):140. PMC: 6161470. DOI: 10.1186/s12943-018-0889-7. View

11.

Du W, Hu J, Hu R, Yang M, Peng Y, Zhang Z . circ0101675 promotes malignant process via sponging miR-1278 and upregulating WNT3A/5A in non-small cell lung cancer. J Cancer. 2021; 12(14):4209-4217. PMC: 8176403. DOI: 10.7150/jca.57255. View

12.

Hansen T, Jensen T, Clausen B, Bramsen J, Finsen B, Damgaard C . Natural RNA circles function as efficient microRNA sponges. Nature. 2013; 495(7441):384-8. DOI: 10.1038/nature11993. View

13.

Chen P, Yao Y, Yang N, Gong L, Kong Y, Wu A . Circular RNA circCTNNA1 promotes colorectal cancer progression by sponging miR-149-5p and regulating FOXM1 expression. Cell Death Dis. 2020; 11(7):557. PMC: 7376054. DOI: 10.1038/s41419-020-02757-7. View

14.

Pfefferle A, Mailloux R, Adjeitey C, Harper M . Glutathionylation of UCP2 sensitizes drug resistant leukemia cells to chemotherapeutics. Biochim Biophys Acta. 2012; 1833(1):80-9. DOI: 10.1016/j.bbamcr.2012.10.006. View

15.

Derdak Z, Mark N, Beldi G, Robson S, Wands J, Baffy G . The mitochondrial uncoupling protein-2 promotes chemoresistance in cancer cells. Cancer Res. 2008; 68(8):2813-9. PMC: 2386271. DOI: 10.1158/0008-5472.CAN-08-0053. View

16.

Yu Z, Tang H, Chen S, Xie Y, Shi L, Xia S . Exosomal LOC85009 inhibits docetaxel resistance in lung adenocarcinoma through regulating ATG5-induced autophagy. Drug Resist Updat. 2023; 67:100915. DOI: 10.1016/j.drup.2022.100915. View

17.

Wang Z, Yang L, Wu P, Li X, Tang Y, Ou X . The circROBO1/KLF5/FUS feedback loop regulates the liver metastasis of breast cancer by inhibiting the selective autophagy of afadin. Mol Cancer. 2022; 21(1):29. PMC: 8785480. DOI: 10.1186/s12943-022-01498-9. View

18.

Chen L . The biogenesis and emerging roles of circular RNAs. Nat Rev Mol Cell Biol. 2016; 17(4):205-11. DOI: 10.1038/nrm.2015.32. View

19.

Chen D, Wang R, Yu C, Cao F, Zhang X, Yan F . FOX-A1 contributes to acquisition of chemoresistance in human lung adenocarcinoma via transactivation of SOX5. EBioMedicine. 2019; 44:150-161. PMC: 6607090. DOI: 10.1016/j.ebiom.2019.05.046. View

20.

Tan S, Sun D, Pu W, Gou Q, Guo C, Gong Y . Circular RNA F-circEA-2a derived from EML4-ALK fusion gene promotes cell migration and invasion in non-small cell lung cancer. Mol Cancer. 2018; 17(1):138. PMC: 6146612. DOI: 10.1186/s12943-018-0887-9. View