PULMONOLOGY / BASIC RESEARCH
Circular RNA circ_0001421 contributes to colony formation, migration, invasion and glycolysis of non-small cell lung cancer via the miR-409-3p/TMEM14A axis
More details
Hide details
1
Department of Respiratory, Xiantao First People’s Hospital Affiliated to Changjiang
University, Xiantao, Hubei, China
2
Department of Oncology, Xiantao First People’s Hospital Affiliated to Changjiang
University, Xiantao, Hubei, China
Submission date: 2019-12-26
Final revision date: 2020-03-26
Acceptance date: 2020-04-10
Online publication date: 2021-03-18
Publication date: 2026-01-16
Corresponding author
Feng Rong
Department of Respiratory, Xiantao First People's Hospital Affiliated to Changjiang University, No. 29 Middle Section of The Mianzhou Avenue, Nancheng New District, Xiantao433000, Hubei, China.
Arch Med Sci 2025;21(6):2692-2709
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Accumulating evidence testifies to the considerably significant roles of circular RNAs (circRNAs) in non-small cell lung cancer (NSCLC).
This report describes the exploration of the molecular mechanism of circRNA_0001421 (circ_0001421) in NSCLC.
Material and methods:
The relative levels of circ_0001421, microRNA-409-3p
(miR-409-3p) and transmembrane protein 14A (TMEM14A) were assayed
through quantitative real-time polymerase chain reaction (qRT-PCR). Cell colony formation ability was detected by colony formation assay. Transwell assay was exploited for assessing cell migration and invasion. Glycolysis was
evaluated via ECAR measurement, glucose consumption, lactate production
and protein detection. The protein levels were examined using Western blot.
The target combination between miR-409-3p and circ_0001421 or TMEM14A
was analyzed by dual-luciferase reporter assay. Xenotransplantation assay
was applied for estimating the effect of circ_0001421 on NSCLC in 10 mice.
Results:
Circ_0001421 was up-regulated in NSCLC tissues and cells.
Down-regulation of circ_0001421 suppressed colony formation, migration,
invasion and glycolysis of NSCLC cells. Circ_0001421 could sponge microRNA-409-3p (miR-409-3p) and miR-409-3p inhibition relieved the effects
of circ_0001421 knockdown on NSCLC cells. MiR-409-3p targeted transmembrane protein 14A (TMEM14A) and circ_0001421 modulated TMEM14A
expression via targeting miR-409-3p. Overexpression of miR-409-3p suppressed NSCLC progression by inhibiting TMEM14A. Circ_0001421 depression restrained tumor growth of NSCLC by the miR-409-3p/TMEM14A axis
in vivo.
Conclusions:
Circ_0001421 facilitated the development of NSCLC via the
regulation of the miR-409-3p/TMEM14A axis. Circ_0001421 may be a promising therapeutic target in NSCLC.
REFERENCES (45)
1.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68: 394-424.
2.
Gridelli C, Rossi A, Carbone DP, et al. Non-small-cell lung cancer. Nat Rev Dis Primers 2015; 1: 15009.
3.
Nadal E, Massuti B, Domine M, Garcia-Campelo R, Cobo M, Felip E. Immunotherapy with checkpoint inhibitors in non-small cell lung cancer: insights from long-term survivors. Cancer Immunol Immunother 2019; 68: 341-52.
4.
Masood A, Kancha RK, Subramanian J. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in non-small cell lung cancer harboring uncommon EGFR mutations: focus on afatinib. Semin Oncol 2019; 46: 271-83.
5.
Rosas G, Ruiz R, Araujo JM, Pinto JA, Mas L. ALK rearrangements: biology, detection and opportunities of therapy in non-small cell lung cancer. Crit Rev Oncol Hematol 2019; 136: 48-55.
6.
Arbour KC, Riely GJ. Systemic therapy for locally advanced and metastatic non-small cell lung cancer: a review. JAMA 2019; 322: 764-74.
7.
Chen Y, Lu L, Feng B, et al. Non-coding RNAs as emerging regulators of epithelial to mesenchymal transition in non-small cell lung cancer. Oncotarget 2017; 8: 36787-99.
8.
Wei MM, Zhou GB. Long non-coding RNAs and their roles in non-small-cell lung cancer. Genomics Proteomics Bioinformatics 2016; 14: 280-8.
9.
Wilusz JE, Sharp PA. Molecular biology. A circuitous route to noncoding RNA. Science 2013; 340: 440-1.
10.
Memczak S, Jens M, Elefsinioti A, et al. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature 2013; 495: 333-8.
11.
Guan X, Zong ZH, Liu Y, Chen S, Wang LL, Zhao Y. circPUM1 promotes tumorigenesis and progression of ovarian cancer by sponging miR-615-5p and miR-6753-5p. Mol Ther Nucleic Acids 2019; 18: 882-92.
12.
Wang X, Wang X, Li W, Zhang Q, Chen J, Chen T. Up-regulation of hsa_circ_0000517 predicts adverse prognosis of hepatocellular carcinoma. Front Oncol 2019; 9: 1105.
13.
Liu W, Ma W, Yuan Y, Zhang Y, Sun S. Circular RNA hsa_circRNA_103809 promotes lung cancer progression via facilitating ZNF121-dependent MYC expression by sequestering miR-4302. Biochem Biophys Res Commun 2018; 500: 846-51.
14.
Jin M, Shi C, Yang C, Liu J, Huang G. Upregulated circRNA ARHGAP10 predicts an unfavorable prognosis in NSCLC through regulation of the miR-150-5p/GLUT-1 axis. Mol Ther Nucleic Acids 2019; 18: 219-31.
15.
Mendell JT, Olson EN. MicroRNAs in stress signaling and human disease. Cell 2012; 148: 1172-87.
16.
Hammond SM. An overview of microRNAs. Adv Drug Deliv Rev 2015; 87: 3-14.
17.
Yin Z, Xu M, Li P. miRNA-221 acts as an oncogenic role by directly targeting TIMP2 in non-small-cell lung carcinoma. Gene 2017; 620: 46-53.
18.
Ma HP, Kong WX, Li XY, Li W, Zhang Y, Wu Y. miRNA-223 is an anticancer gene in human non-small cell lung cancer through the PI3K/AKT pathway by targeting EGFR. Oncol Rep 2019; 41: 1549-59.
19.
Song Q, Ji Q, Xiao J, et al. miR-409 Inhibits human non-small-cell lung cancer progression by directly targeting SPIN1. Mol Ther Nucleic Acids 2018; 13: 154-63.
20.
Qu R, Chen X, Zhang C. LncRNA ZEB1-AS1/miR-409-3p/ZEB1 feedback loop is involved in the progression of non-small cell lung cancer. Biochem Biophys Res Commun 2018; 507: 450-6.
21.
Zhang Q, Chen X, Zhang X, Zhan J, Chen J. Knockdown of TMEM14A expression by RNAi inhibits the proliferation and invasion of human ovarian cancer cells. Biosci Rep 2016; 36: e00298.
22.
An J, Shi H, Zhang N, Song S. Elevation of circular RNA circ_0003645 forecasts unfavorable prognosis and facilitates cell progression via miR-1179/TMEM14A pathway in non-small cell lung cancer. Biochem Biophys Res Commun 2019; 511: 921-5.
23.
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 2001; 25: 402-8.
24.
Liu L, Wang Y, Bai R, Yang K, Tian Z. MiR-186 inhibited aerobic glycolysis in gastric cancer via HIF-1alpha regulation. Oncogenesis 2016; 5: e224.
25.
Taylor SC, Berkelman T, Yadav G, Hammond M. A defined methodology for reliable quantification of Western blot data. Mol Biotechnol 2013; 55: 217-26.
26.
Jiao L, Wang S, Zheng Y, et al. Betulinic acid suppresses breast cancer aerobic glycolysis via caveolin-1/NF-kappaB/c-Myc pathway. Biochem Pharmacol 2019; 161: 149-62.
27.
Brandi J, Cecconi D, Cordani M, et al. The antioxidant uncoupling protein 2 stimulates hnRNPA2/B1, GLUT1 and PKM2 expression and sensitizes pancreas cancer cells to glycolysis inhibition. Free Radic Biol Med 2016; 101: 305-16.
28.
Chen L, Zhang S, Wu J, et al. circRNA_100290 plays a role in oral cancer by functioning as a sponge of the miR-29 family. Oncogene 2017; 36: 4551-61.
29.
Zhao F, Chen CW, Yang WW, et al. Hsa_circRNA_0059655 plays a role in salivary adenoid cystic carcinoma by functioning as a sponge of miR-338-3p. Cell Mol Biol (Noisy-le-grand) 2018; 64: 100-6.
30.
Yang J, Cong X, Ren M, et al. Circular RNA hsa_circRNA_0007334 is predicted to promote MMP7 and COL1A1 expression by functioning as a miRNA sponge in pancreatic ductal adenocarcinoma. J Oncol 2019; 2019: 7630894.
31.
Hassanlou M, Soltani BM, Medlej A, Kay M, Mowla SJ. Hsa-miR-6165 downregulates insulin-like growth factor-1 receptor (IGF-1R) expression and enhances apoptosis in SW480 cells. Biol Chem 2020; 401: 477-85.
32.
Pu M, Chen J, Tao Z, et al. Regulatory network of miRNA on its target: coordination between transcriptional and post-transcriptional regulation of gene expression. Cell Mol Life Sci 2019; 76: 441-51.
33.
Fujimoto J, Wistuba II. Current concepts on the molecular pathology of non-small cell lung carcinoma. Semin Diagn Pathol 2014; 31: 306-13.
34.
Prabhu VV, Devaraj N. Epidermal growth factor receptor tyrosine kinase: a potential target in treatment of non-small-cell lung carcinoma. J Environ Pathol Toxicol Oncol 2017; 36: 151-8.
35.
Wang Y, Li H, Lu H, Qin Y. Circular RNA SMARCA5 inhibits the proliferation, migration, and invasion of non-small cell lung cancer by miR-19b-3p/HOXA9 axis. Onco Targets Ther 2019; 12: 7055-65.
36.
Huang MS, Liu JY, Xia XB, et al. Hsa_circ_0001946 inhibits lung cancer progression and mediates cisplatin sensitivity in non-small cell lung cancer via the nucleotide excision repair signaling pathway. Front Oncol 2019; 9: 508.
37.
Gao P, Wang Z, Hu Z, Jiao X, Yao Y. Circular RNA circ_0074027 indicates a poor prognosis for NSCLC patients and modulates cell proliferation, apoptosis, and invasion via miR-185-3p mediated BRD4/MADD activation. J Cell Biochem 2020; 121: 2632-42.
38.
Zhang H, Wang X, Hu B, Zhang F, Wei H, Li L. Circular RNA ZFR accelerates non-small cell lung cancer progression by acting as a miR-101-3p sponge to enhance CUL4B expression. Artif Cells Nanomed Biotechnol 2019; 47: 3410-6.
39.
Ganapathy-Kanniappan S, Geschwind JF. Tumor glycolysis as a target for cancer therapy: progress and prospects. Mol Cancer 2013; 12: 152.
40.
Ganapathy-Kanniappan S. Molecular intricacies of aerobic glycolysis in cancer: current insights into the classic metabolic phenotype. Crit Rev Biochem Mol Biol 2018; 53: 667-82.
41.
Wu L, Zhang Y, Huang Z, et al. MiR-409-3p inhibits cell proliferation and invasion of osteosarcoma by targeting zinc-finger E-box-binding homeobox-1. Front Pharmacol 2019; 10: 137.
42.
Zhang G, Liu Z, Xu H, Yang Q. miR-409-3p suppresses breast cancer cell growth and invasion by targeting Akt1. Biochem Biophys Res Commun 2016; 469: 189-95.
43.
Xiao Y. Construction of a circRNA-miRNA-mRNA network to explore the pathogenesis and treatment of pancreatic ductal adenocarcinoma. J Cell Biochem 2020; 121: 394-406.
44.
Guan YJ, Ma JY, Song W. Identification of circRNA-miRNA-mRNA regulatory network in gastric cancer by analysis of microarray data. Cancer Cell Int 2019; 19: 183.
45.
Liu K, Guo Y, Zheng K, et al. Identification of the circRNA-miRNA-mRNA regulatory network of Hsp90 inhibitor-induced cell death in colorectal cancer by integrated analysis. Gene 2020; 727: 144232.