Display options
Cite
Yu J, Chen X, Li J, et al. CircRUNX1 functions as an oncogene in colorectal cancer by regulating circRUNX1/miR-485-5p/SLC38A1 axis. Eur J Clin Invest. 2021;51(7):e13540doi: 10.1111/eci.13540.
Yu, J., Chen, X., Li, J., & Wang, F. (2021). CircRUNX1 functions as an oncogene in colorectal cancer by regulating circRUNX1/miR-485-5p/SLC38A1 axis. European journal of clinical investigation, 51(7), e13540. https://doi.org/10.1111/eci.13540
Yu, Juan, et al. "CircRUNX1 functions as an oncogene in colorectal cancer by regulating circRUNX1/miR-485-5p/SLC38A1 axis." European journal of clinical investigation vol. 51,7 (2021): e13540. doi: https://doi.org/10.1111/eci.13540
Yu J, Chen X, Li J, Wang F. CircRUNX1 functions as an oncogene in colorectal cancer by regulating circRUNX1/miR-485-5p/SLC38A1 axis. Eur J Clin Invest. 2021 Jul;51(7):e13540. doi: 10.1111/eci.13540. Epub 2021 Mar 26. PMID: 33769559.
Copy Download .nbib Format: NLM
Share it on

Eur J Clin Invest. 2021 Jul;51(7):e13540. doi: 10.1111/eci.13540. Epub 2021 Mar 26.

CircRUNX1 functions as an oncogene in colorectal cancer by regulating circRUNX1/miR-485-5p/SLC38A1 axis.

European journal of clinical investigation

Juan Yu, Xiaoguang Chen, Jing Li, Furang Wang

Affiliations

  1. Department of Endoscopic Diagnosis and Treatment Center, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China.

PMID: 33769559 DOI: 10.1111/eci.13540

Abstract

BACKGROUND: Circular RNAs (circRNAs) have emerged as vital regulators in human cancers, including colorectal cancer (CRC). In this study, we aimed to explore the roles of circRUNX1 in CRC.

METHODS: The levels of circRUNX1, RUNX1 mRNA, solute carrier family 38 member 1 (SLC38A1) mRNA and microRNA-485-5p (miR-485-5p) were determined by quantitative real-time polymerase chain reaction (qRT-PCR) analysis. The protein level of SLC38A1 was measured by Western blot assay. Cell colony formation, migration, invasion and apoptosis were assessed by colony formation assay, wound-healing assay, Transwell assay and flow cytometry analysis, respectively. The interaction between miR-485-5p and circRUNX1 or SLC38A1 was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The levels of extracellular glutamine, intracellular glutamate and α-ketoglutarate (α-KG) were measured with specific kits. The functional role of circRUNX1 in CRC development in vivo was explored by murine xenograft model assay.

RESULTS: CircRUNX1 was upregulated in CRC tissues and cells compared with normal tissues and cells. CircRUNX1 deficiency restrained CRC cell colony formation, migration, invasion and glutaminolysis and induced apoptosis in vitro as well as blocked tumour growth in vivo. CircRUNX1 directly sponged miR-485-5p, which negatively modulated SLC38A1 expression in CRC cells. The effects of circRUNX1 knockdown on CRC cell colony formation, migration, invasion, apoptosis and glutaminolysis were reversed by miR-485-5p inhibition. Moreover, miR-485-5p overexpression repressed the malignant behaviours of CRC cells, with SLC38A1 elevation overturned the impacts.

CONCLUSION: CircRUNX1 promoted CRC cell growth, metastasis and glutamine metabolism and repressed apoptosis by elevating SLC38A1 through sponging miR-485-5p, which might provide a novel target for CRC treatment.

© 2021 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.

Keywords: CRC; SLC38A1; circRUNX1; miR-485-5p

References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7-34. - PubMed
  2. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127(12):2893-2917. - PubMed
  3. McQuade RM, Stojanovska V, Bornstein JC, Nurgali K. Colorectal cancer chemotherapy: the evolution of treatment and new approaches. Curr Med Chem. 2017;24(15):1537-1557. - PubMed
  4. Kanas GP, Taylor A, Primrose JN, et al. Survival after liver resection in metastatic colorectal cancer: review and meta-analysis of prognostic factors. Clin Epidemiol. 2012;4:283-301. - PubMed
  5. Manfredi S, Lepage C, Hatem C, Coatmeur O, Faivre J, Bouvier AM. Epidemiology and management of liver metastases from colorectal cancer. Ann Surg. 2006;244(2):254-259. - PubMed
  6. Chen LL, Yang L. Regulation of circRNA biogenesis. RNA Biol. 2015;12(4):381-388. - PubMed
  7. Hansen TB, Jensen TI, Clausen BH, et al. Natural RNA circles function as efficient microRNA sponges. Nature. 2013;495(7441):384-388. - PubMed
  8. Taulli R, Loretelli C, Pandolfi PP. From pseudo-ceRNAs to circ-ceRNAs: a tale of cross-talk and competition. Nat Struct Mol Biol. 2013;20(5):541-543. - PubMed
  9. Lei M, Zheng G, Ning Q, Zheng J, Dong D. Translation and functional roles of circular RNAs in human cancer. Mol Cancer. 2020;19(1):30. - PubMed
  10. Geng Y, Zheng X, Hu W, et al. Hsa_circ_0009361 acts as the sponge of miR-582 to suppress colorectal cancer progression by regulating APC2 expression. Clin Sci (Lond). 2019;133(10):1197-1213. - PubMed
  11. Yong W, Zhuoqi X, Baocheng W, Dongsheng Z, Chuan Z, Yueming S. Hsa_circ_0071589 promotes carcinogenesis via the miR-600/EZH2 axis in colorectal cancer. Biomed Pharmacother. 2018;102:1188-1194. - PubMed
  12. Jian X, He H, Zhu J, et al. Hsa_circ_001680 affects the proliferation and migration of CRC and mediates its chemoresistance by regulating BMI1 through miR-340. Mol Cancer. 2020;19(1):20. - PubMed
  13. Farazi TA, Spitzer JI, Morozov P, Tuschl T. miRNAs in human cancer. J Pathol. 2011;223(2):102-115. - PubMed
  14. Lou C, Xiao M, Cheng S, et al. MiR-485-3p and miR-485-5p suppress breast cancer cell metastasis by inhibiting PGC-1alpha expression. Cell Death Dis. 2016;7:e2159. - PubMed
  15. Zhang Y, Hu J, Zhou W, Gao H. LncRNA FOXD2-AS1 accelerates the papillary thyroid cancer progression through regulating the miR-485-5p/KLK7 axis. J Cell Biochem. 2019;120(5):7952-7961. - PubMed
  16. Duan J, Zhang H, Li S, et al. The role of miR-485-5p/NUDT1 axis in gastric cancer. Cancer Cell Int. 2017;17:92. - PubMed
  17. Wang R, Zuo X, Wang K, et al. MicroRNA-485-5p attenuates cell proliferation in glioma by directly targeting paired box 3. Am J Cancer Res. 2018;8(12):2507-2517. - PubMed
  18. Liu J, Zhang J, Wang Z, Xi J, Bai L, Zhang Y. Knockdown of circAPLP2 inhibits progression of colorectal cancer by regulating miR-485-5p/FOXK1 axis. Cancer Biother Radiopharm. 2020. - PubMed
  19. Hu XX, Xu XN, He BS, et al. microRNA-485-5p functions as a tumor suppressor in colorectal cancer cells by targeting CD147. J Cancer. 2018;9(15):2603-2611. - PubMed
  20. Broer S. The SLC38 family of sodium-amino acid co-transporters. Pflugers Arch. 2014;466(1):155-172. - PubMed
  21. Broer A, Rahimi F, Broer S. Deletion of amino acid transporter ASCT2 (SLC1A5) reveals an essential role for transporters SNAT1 (SLC38A1) and SNAT2 (SLC38A2) to sustain glutaminolysis in cancer cells. J Biol Chem. 2016;291(25):13194-13205. - PubMed
  22. Zhou FF, Xie W, Chen SQ, et al. SLC38A1 promotes proliferation and migration of human colorectal cancer cells. J Huazhong Univ Sci Technolog Med Sci. 2017;37(1):30-36. - PubMed
  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(4):402-408. - PubMed
  24. Jiang Y, Wang X, Zhang J, Lai R. MicroRNA-599 suppresses glioma progression by targeting RAB27B. Oncol Lett. 2018;16(1):1243-1252. - PubMed
  25. Chang P, Wang F, Li Y. Hsa_circ_0000673 is down-regulated in gastric cancer and inhibits the proliferation and invasion of tumor cells by targeting miR-532-5p. Biosci Rep. 2018;38(5):BSR20180538. - PubMed
  26. Cai H, Hu B, Ji L, Ruan X, Zheng Z. Hsa_circ_0103809 promotes cell proliferation and inhibits apoptosis in hepatocellular carcinoma by targeting miR-490-5p/SOX2 signaling pathway. Am J Transl Res. 2018;10(6):1690-1702. - PubMed
  27. Li J, Zhen L, Zhang Y, et al. Circ-104916 is downregulated in gastric cancer and suppresses migration and invasion of gastric cancer cells. Onco Targets Ther. 2017;10:3521-3529. - PubMed
  28. Sun H, Xi P, Sun Z, et al. Circ-SFMBT2 promotes the proliferation of gastric cancer cells through sponging miR-182-5p to enhance CREB1 expression. Cancer Manag Res. 2018;10:5725-5734. - PubMed
  29. Zhang L, Cheng H, Yue Y, Li S, Zhang D, He R. H19 knockdown suppresses proliferation and induces apoptosis by regulating miR-148b/WNT/beta-catenin in ox-LDL -stimulated vascular smooth muscle cells. J Biomed Sci. 2018;25(1):11. - PubMed
  30. Li P, Chen H, Chen S, et al. Circular RNA 0000096 affects cell growth and migration in gastric cancer. Br J Cancer. 2017;116(5):626-633. - PubMed
  31. Broer S, Brookes N. Transfer of glutamine between astrocytes and neurons. J Neurochem. 2001;77(3):705-719. - PubMed
  32. Zhang Z, Song N, Wang Y, et al. Analysis of differentially expressed circular RNAs for the identification of a coexpression RNA network and signature in colorectal cancer. J Cell Biochem. 2019;120(4):6409-6419. - PubMed
  33. Chen S, Zhang L, Su Y, Zhang X. Screening potential biomarkers for colorectal cancer based on circular RNA chips. Oncol Rep. 2018;39(6):2499-2512. - PubMed
  34. Ren C, Zhang Z, Wang S, Zhu W, Zheng P, Wang W. Circular RNA hsa_circ_0001178 facilitates the invasion and metastasis of colorectal cancer through upregulating ZEB1 via sponging multiple miRNAs. Biol Chem. 2020;401(4):487-496. - PubMed
  35. Jin C, Wang A, Liu L, Wang G, Li G. Hsa_circ_0136666 promotes the proliferation and invasion of colorectal cancer through miR-136/SH2B1 axis. J Cell Physiol. 2019;234(5):7247-7256. - PubMed
  36. Chen ZL, Li XN, Ye CX, Chen HY, Wang ZJ. Elevated levels of circRUNX1 in colorectal cancer promote cell growth and metastasis via miR-145-5p/IGF1 signalling. Onco Targets Ther. 2020;13:4035-4048. - PubMed
  37. Sanchez-Tillo E, Liu Y, de Barrios O, et al. EMT-activating transcription factors in cancer: beyond EMT and tumor invasiveness. Cell Mol Life Sci. 2012;69(20):3429-3456. - PubMed
  38. Adams JM, Cory S. The BCL-2 arbiters of apoptosis and their growing role as cancer targets. Cell Death Differ. 2018;25(1):27-36. - PubMed
  39. Salam AAA, Nayek U, Sunil D. Homology modeling and docking studies of Bcl-2 and Bcl-xL with small molecule inhibitors: identification and functional studies. Curr Top Med Chem. 2018;18(31):2633-2663. - PubMed
  40. Pan Y, Qin J, Sun H, Xu T, Wang S, He B. MiR-485-5p as a potential biomarker and tumor suppressor in human colorectal cancer. Biomark Med. 2020;14(3):239-248. - PubMed
  41. Wang X, Tao G, Huang D, Liang S, Zheng D. Circular RNA NOX4 promotes the development of colorectal cancer via the microRNA4855p/CKS1B axis. Oncol Rep. 2020;44(5):2009-2020. - PubMed
  42. Wang S, Du H, Sun P. Long noncoding RNA NEAT1 contributes to the tumorigenesis of colorectal cancer through regulating SLC38A1 expression by sponging miR-138. Cancer Biother Radiopharm. 2020. - PubMed
  43. Hensley CT, Wasti AT, DeBerardinis RJ. Glutamine and cancer: cell biology, physiology, and clinical opportunities. J Clin Invest. 2013;123(9):3678-3684. - PubMed
  44. Yang L, Venneti S, Nagrath D. Glutaminolysis: a hallmark of cancer metabolism. Annu Rev Biomed Eng. 2017;19:163-194. - PubMed

Publication Types