CircPKM2 Aggravates the Progression of Non-small Cell Lung Cancer by Regulating MTDH Via MiR-1298-5p

Overview

Journal Thorac Cancer

Specialties Oncology
Pulmonary Medicine

Date 2023 Sep 7

PMID 37675591

Authors

Shuhua Gao

Tingting Gao

Li Feng

Haixia Li

Guogang Dong

Shan Yang

Affiliations

Soon will be listed here.

Abstract

Background: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer with high morbidity and mortality. The role of dysregulated circular RNAs (circRNAs) in human diseases are receiving more and more attention. In this study, we focused on the role and mechanism of circPKM2 in the progression of NSCLC.

Methods: The expression levels of circPKM2, microRNA-1298-5p (miR-1298-5p) and metadherin (MTDH) in NSCLC were measured by real-time quantitative PCR (qRT-PCR) or Western blot. Cell counting kit-8 (CCK-8), colony formation, 5-ethynyl-2'-deoxyuridine (EdU) staining, flow cytometry, transwell and tube formation assays were conducted to evaluate the effects of circPKM2 on malignant phenotypes of NSCLC. Western blot was used to measure related marker protein levels.

Results: CircPKM2 and MTDH were highly expressed in NSCLC tissues and cells, while miR-1298-5p was downregulated. CircPKM2 knockdown effectively suppressed cell proliferation, migration, invasion and tube formation whereas induced apoptosis in vitro. CircPKM2 had a potential targeting site with miR-1298-5p and negatively regulated the expression of miR-1298-5p. MiR-1298-5p inhibitor reversed the effect of circPKM2 knockdown on the progression of NSCLC. CircPKM2 induced MTDH expression via sponging miR-1298-5p to promote the progression of NSCLC. MiR-1298-5p directly targeted MTDH, and the addition of MTDH partially attenuated the inhibition of miR-1298-5p on the progression of NSCLC. In addition, the downregulation of circPKM2 significantly slowed down the growth of xenograft tumors in vivo.

Conclusion: Our findings demonstrated that circPKM2 mediated NSCLC progression via regulating miR-1298-5p/MTDH axis, providing a novel therapeutic target for NSCLC.

Citing Articles

Roles and mechanisms of circular RNA in respiratory system cancers.

Yang N, Jiao M, Zhang Y, Mo S, Wang L, Liang J Front Oncol. 2024; 14:1430051.

PMID: 39077467 PMC: 11284073. DOI: 10.3389/fonc.2024.1430051.

CircPKM2 aggravates the progression of non-small cell lung cancer by regulating MTDH via miR-1298-5p.

Gao S, Gao T, Feng L, Li H, Dong G, Yang S Thorac Cancer. 2023; 14(30):3020-3031.

PMID: 37675591 PMC: 10599976. DOI: 10.1111/1759-7714.15092.

References

Li Y, Xu C, He C, Pu H, Liu J, Wang Y . circMTDH.4/miR-630/AEG-1 axis participates in the regulation of proliferation, migration, invasion, chemoresistance, and radioresistance of NSCLC. Mol Carcinog. 2019; 59(2):141-153. DOI: 10.1002/mc.23135. View

Lai X, Li J, Tang L, Chen W, Zhang L, Xiong L . MiRNAs and LncRNAs: Dual Roles in TGF-β Signaling-Regulated Metastasis in Lung Cancer. Int J Mol Sci. 2020; 21(4). PMC: 7072809. DOI: 10.3390/ijms21041193. View

Xue M, Hong W, Jiang J, Zhao F, Gao X . Circular RNA circ-LDLRAD3 serves as an oncogene to promote non-small cell lung cancer progression by upregulating SLC1A5 through sponging miR-137. RNA Biol. 2020; 17(12):1811-1822. PMC: 7714484. DOI: 10.1080/15476286.2020.1789819. View

Ning Z, Tian Y, Li Y, Zhao X, Zhang J, Wang C . Exosomal circ_0007385 enhances non-small cell lung cancer cell proliferation and stemness via regulating miR-1253/FAM83A axis. Anticancer Drugs. 2021; 33(1):61-74. DOI: 10.1097/CAD.0000000000001103. View

Guan H, Sun C, Gu Y, Li J, Ji J, Zhu Y . Circular RNA circ_0003028 contributes to tumorigenesis by regulating GOT2 via miR-1298-5p in non-small cell lung cancer. Bioengineered. 2021; 12(1):2326-2340. PMC: 8806680. DOI: 10.1080/21655979.2021.1935064. View

Shangguan H, Feng H, Lv D, Wang J, Tian T, Wang X . Circular RNA circSLC25A16 contributes to the glycolysis of non-small-cell lung cancer through epigenetic modification. Cell Death Dis. 2020; 11(6):437. PMC: 7280231. DOI: 10.1038/s41419-020-2635-5. View

Ma Z, Wei K, Yang F, Guo Z, Pan C, He Y . Tumor-derived exosomal miR-3157-3p promotes angiogenesis, vascular permeability and metastasis by targeting TIMP/KLF2 in non-small cell lung cancer. Cell Death Dis. 2021; 12(9):840. PMC: 8426367. DOI: 10.1038/s41419-021-04037-4. View

Chen W, Zheng R, Baade P, Zhang S, Zeng H, Bray F . Cancer statistics in China, 2015. CA Cancer J Clin. 2016; 66(2):115-32. DOI: 10.3322/caac.21338. View

Han B, Chao J, Yao H . Circular RNA and its mechanisms in disease: From the bench to the clinic. Pharmacol Ther. 2018; 187:31-44. DOI: 10.1016/j.pharmthera.2018.01.010. View

10.

Guo C, Wang H, Jiang H, Qiao L, Wang X . Circ_0011292 Enhances Paclitaxel Resistance in Non-Small Cell Lung Cancer by Regulating miR-379-5p/TRIM65 Axis. Cancer Biother Radiopharm. 2020; 37(2):84-95. DOI: 10.1089/cbr.2019.3546. View

11.

Zhang S, Li G, Liu C, Lu S, Jing Q, Chen X . miR-30e-5p represses angiogenesis and metastasis by directly targeting AEG-1 in squamous cell carcinoma of the head and neck. Cancer Sci. 2019; 111(2):356-368. PMC: 7004514. DOI: 10.1111/cas.14259. View

12.

Shen W, Zhang X, Fu X, Fan J, Luan J, Cao Z . A novel and promising therapeutic approach for NSCLC: recombinant human arginase alone or combined with autophagy inhibitor. Cell Death Dis. 2017; 8(3):e2720. PMC: 5386540. DOI: 10.1038/cddis.2017.137. View

13.

Chen L, Heikkinen L, Wang C, Yang Y, Sun H, Wong G . Trends in the development of miRNA bioinformatics tools. Brief Bioinform. 2018; 20(5):1836-1852. PMC: 7414524. DOI: 10.1093/bib/bby054. View

14.

Lemjabbar-Alaoui H, Hassan O, Yang Y, Buchanan P . Lung cancer: Biology and treatment options. Biochim Biophys Acta. 2015; 1856(2):189-210. PMC: 4663145. DOI: 10.1016/j.bbcan.2015.08.002. View

15.

Yu X, Fu X, Zhang X, Bai C, Wang Y . Circ_0001658 regulates gefitinib resistance of non-small cell lung cancer through miR-409-3p/TWIST1 axis. Anticancer Drugs. 2021; 33(2):158-166. DOI: 10.1097/CAD.0000000000001257. View

16.

Qin C, Lu R, Yuan M, Zhao R, Zhou H, Fan X . Circular RNA 0006349 Augments Glycolysis and Malignance of Non-small Cell Lung Cancer Cells Through the microRNA-98/MKP1 Axis. Front Cell Dev Biol. 2021; 9:690307. PMC: 8484757. DOI: 10.3389/fcell.2021.690307. View

17.

Shen M, Xie S, Rowicki M, Michel S, Wei Y, Hang X . Therapeutic Targeting of Metadherin Suppresses Colorectal and Lung Cancer Progression and Metastasis. Cancer Res. 2020; 81(4):1014-1025. PMC: 8026491. DOI: 10.1158/0008-5472.CAN-20-1876. View

18.

He W, Qin M, Cai Y, Gao X, Cao S, Wang Z . Downregulation of HOXC6 by miR-27a ameliorates gefitinib resistance in non-small cell lung cancer. Am J Cancer Res. 2021; 11(9):4329-4346. PMC: 8493406. View

19.

Du Z, Wu J, Wang J, Liang Y, Zhang S, Shang Z . MicroRNA-1298 is downregulated in non-small cell lung cancer and suppresses tumor progression in tumor cells. Diagn Pathol. 2019; 14(1):132. PMC: 6894281. DOI: 10.1186/s13000-019-0911-4. View

20.

Hong W, Xue M, Jiang J, Zhang Y, Gao X . Circular RNA circ-CPA4/ let-7 miRNA/PD-L1 axis regulates cell growth, stemness, drug resistance and immune evasion in non-small cell lung cancer (NSCLC). J Exp Clin Cancer Res. 2020; 39(1):149. PMC: 7397626. DOI: 10.1186/s13046-020-01648-1. View