Original Articles

Turkish Journal of Gastroenterology

hsa_circ_0007376 Promotes Gastric Cancer Proliferation and Malignant Metastasis by Enhancing the Stability of IGF2BP3

Main Article Content

LinHu Liang
Ting Han
ZhengRong Zhang
ZhengWu Cheng
HaoRan Li

Abstract

Background/Aims: This study investigated the action of hsa_circ_0007376 in promoting the proliferation and metastasis of gastric cancer (GC).


Materials and Methods: hsa_circ_0007376 was detected in GC tissues and cells by quantitative reverse transcription polymerase chain reaction. RNase R digestion, nucleoplasmic separation, and actinomycin D assays were conducted to detect the presence of hsa_circ_0007376 and its cyclic nature. The tumor-promoting effect of hsa_circ_0007376 in GC cells was verified by CCK-8, colony formation, wound healing, and Transwell assays. An interplay between hsa_circ_0007376 and insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) was confirmed by FISH, RIP, and RNA pull-down experiments. The function of hsa_circ_0007376 on GC proliferation and metastasis was evaluated in vivo in a GC xenograft mouse model.


Results: hsa_circ_0007376 was highly expressed in GC. hsa_circ_0007376 was associated with lymphatic metastasis, Tumor node metastasis (TNM) stage, and tumor size in GC. When hsa_circ_0007376 was knocked down, GC cells were prevented from proliferating, migrating, and invading, as well as being prevented from metastasizing. hsa_circ_0007376 was able to bind to IGF2BP3, thereby promoting GC.


Conclusion: hsa_circ_0007376 may play a role in GC by interacting and enhancing the stability of the IGF2BP3 protein.

Cite this article as: Liang L, Han T, Zhang Z, Cheng Z, Li H. hsa_circ_0007376 promotes gastric cancer proliferation and malignant metastasis by enhancing the stability of IGF2BP3. Turk J Gastroenterol. Published online May 20, 2025. doi 10.5152/tjg.2025.24491.

Article Details

References

1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-249. [CrossRef]

2. Li R, Jiang J, Shi H, Qian H, Zhang X, Xu W. CircRNA: a rising star in gastric cancer. Cell Mol Life Sci. 2020;77(9):1661-1680. [CrossRef]

3. Smyth EC, Nilsson M, Grabsch HI, van Grieken NC, Lordick F. Gastric cancer. Lancet. 2020;396(10251):635-648. [CrossRef]

4. Liang X, Zhu J, Li Y, et al. Treatment strategies for metastatic gastric cancer: chemotherapy, palliative surgery or radiotherapy? Future Oncol. 2020;16(5):91-102. [CrossRef]

5. Tang X, Ren H, Guo M, Qian J, Yang Y, Gu C. Review on circular RNAs and new insights into their roles in cancer. Comput Struct Biotechnol J. 2021;19:910-928. [CrossRef]

6. Vo JN, Cieslik M, Zhang Y, et al. The landscape of circular RNA in cancer. Cell. 2019;176(4):869-881.e13. [CrossRef]

7. Zhang Y, Jiang J, Zhang J, et al. CircDIDO1 inhibits gastric cancer progression by encoding a novel DIDO1-529aa protein and regulating PRDX2 protein stability. Mol Cancer. 2021;20(1):101. [CrossRef]

8. Tian M, Chen R, Li T, Xiao B. Reduced expression of circRNA hsa_circ_0003159 in gastric cancer and its clinical significance. J Clin Lab Anal. 2018;32(3):e22281. [CrossRef]

9. Dong J, Zheng Z, Zhou M, et al. EGCG-LYS fibrils-mediated CircMAP2K2 silencing decreases the proliferation and metastasis ability of gastric cancer cells in vitro and in vivo. Adv Sci (Weinh). 2023;10(32):e2304075. [CrossRef]

10. Zhang X, Wang S, Wang H, et al. Circular RNA circNRIP1 acts as a microRNA-149-5p sponge to promote gastric cancer progression via the AKT1/mTOR pathway. Mol Cancer. 2019;18(1):20. [CrossRef]

11. Zhang Y, Liu H, Li W, et al. CircRNA_100269 is downregulated in gastric cancer and suppresses tumor cell growth by targeting miR630. Aging (Albany NY). 2017;9(6):1585-1594. [CrossRef]

12. Zang J, Lu D, Xu A. The interaction of circRNAs and RNA binding proteins: an important part of circRNA maintenance and function. J Neurosci Res. 2020;98(1):87-97. [CrossRef]

13. Xu C, Chen X, Zhang X, et al. RNA-binding protein 39: a promising therapeutic target for cancer. Cell Death Discov. 2021;7(1):214. [CrossRef]

14. Nasiri-Aghdam M, Garcia-Garduño TC, Jave-Suárez LF. CELF family proteins in cancer: highlights on the RNA-binding protein/noncoding RNA regulatory axis. Int J Mol Sci. 2021;22(20):11056. [CrossRef]

15. Hanniford D, Ulloa-Morales A, Karz A, et al. Epigenetic silencing of CDR1as drives IGF2BP3-mediated melanoma invasion and metastasis. Cancer Cell. 2020;37(1):55-70.e15. [CrossRef]

16. Yang F, Ma Q, Huang B, et al. CircNFATC3 promotes the proliferation of gastric cancer through binding to IGF2BP3 and restricting its ubiquitination to enhance CCND1 mRNA stability. J Transl Med. 2023;21(1):402. [CrossRef]

17. Wang Z, Tong D, Han C, et al. Blockade of miR-3614 maturation by IGF2BP3 increases TRIM25 expression and promotes breast cancer cell proliferation. EBiomedicine. 2019;41:357-369. [CrossRef]

18. Gu Y, Niu S, Wang Y, et al. DMDRMR-mediated regulation of m(6)A-modified CDK4 by m(6)A reader IGF2BP3 drives ccRCC progression. Cancer Res. 2021;81(4):923-934. [CrossRef]

19. Zhou Y, Huang T, Siu HL, et al. IGF2BP3 functions as a potential oncogene and is a crucial target of miR-34a in gastric carcinogenesis. Mol Cancer. 2017;16(1):77. [CrossRef]

20. Hong Y, Qin H, Li Y, et al. FNDC3B circular RNA promotes the migration and invasion of gastric cancer cells via the regulation of E-cadherin and CD44 expression. J Cell Physiol. 2019;234(11):19895-19910. [CrossRef]

21. Ma Q, Yang F, Huang B, et al. CircARID1A binds to IGF2BP3 in gastric cancer and promotes cancer proliferation by forming a circARID1A-IGF2BP3-SLC7A5 RNA-protein ternary complex. J Exp Clin Cancer Res. 2022;41(1):251. [CrossRef]

22. Stoll L, Rodríguez-Trejo A, Guay C, et al. A circular RNA generated from an intron of the insulin gene controls insulin secretion. Nat Commun. 2020;11(1):5611. [CrossRef]

23. Xu Y, Yao Y, Gao P, Cui Y. Upregulated circular RNA circ_0030235 predicts unfavorable prognosis in pancreatic ductal adenocarcinoma and facilitates cell progression by sponging miR-1253 and miR-1294. Biochem Biophys Res Commun. 2019;509(1):138-142. [CrossRef]

24. Qiu L, Huang Y, Li Z, et al. Circular RNA profiling identifies circADAMTS13 as a miR-484 sponge which suppresses cell proliferation in hepatocellular carcinoma. Mol Oncol. 2019;13(2):441-455. [CrossRef]

25. Chen RX, Liu HL, Yang LL, et al. Circular RNA circRNA_0000285 promotes cervical cancer development by regulating FUS. Eur Rev Med Pharmacol Sci. 2019;23(20):8771-8778. [CrossRef]

26. Long F, Li L, Xie C, et al. Intergenic CircRNA Circ_0007379 inhibits colorectal cancer progression by modulating miR-320a biogenesis in a KSRP-dependent manner. Int J Biol Sci. 2023;19(12):3781-3803. [CrossRef]

27. Zhou YC, Lao WJ, Xu YL, et al. Upregulation of circRNA_0023685 promotes gastric cancer progression via a circRNA-miRNA-mRNA interaction network. Am J Cancer Res. 2024;14(1):130-144. [CrossRef]

28. Li R, Wang J, Xie Z, et al. CircUSP1 as a novel marker promotes gastric cancer progression via stabilizing HuR to upregulate USP1 and vimentin. Oncogene. 2024;43(14):1033-1049. [CrossRef]

29. Chung HK, Xiao L, Jaladanki KC, Wang JY. Regulation of Paneth cell function by RNA-binding proteins and noncoding RNAs. Cells. 2021;10(8):2107. [CrossRef]

30. Lederer M, Bley N, Schleifer C, Hüttelmaier S. The role of the oncofetal IGF2 mRNA-binding protein 3 (IGF2BP3) in cancer. Semin Cancer Biol. 2014;29:3-12. [CrossRef]

31. Pan Z, Zhao R, Li B, et al. EWSR1-induced circNEIL3 promotes glioma progression and exosome-mediated macrophage immunosuppressive polarization via stabilizing IGF2BP3. Mol Cancer. 2022;21(1):16. [CrossRef]

32. Yu YZ, Lv DJ, Wang C, et al. Hsa_circ_0003258 promotes prostate cancer metastasis by complexing with IGF2BP3 and sponging miR653-5p. Mol Cancer. 2022;21(1):12. [CrossRef]

33. Zhang W, Wang B, Lin Y, et al. hsa_circ_0000231 Promotes colorectal cancer cell growth through upregulation of CCND2 by IGF2BP3/miR-375 dual pathway. Cancer Cell Int. 2022;22(1):27. [CrossRef]

34. Chen C, Yang Z, Tang X. Chemical modifications of nucleic acid drugs and their delivery systems for gene-based therapy. Med Res Rev. 2018;38(3):829-869. [CrossRef]

35. Kulkarni JA, Witzigmann D, Thomson SB, et al. The current landscape of nucleic acid therapeutics. Nat Nanotechnol. 2021;16(6):630-643. [CrossRef]

Similar Articles

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 > >> 

You may also start an advanced similarity search for this article.