Original Articles

Turkish Journal of Gastroenterology

Helicobacter pylori Promoted miR-196a/b-5p Expression and Accelerated Tumorigenesis of the Gastric Mucosa by Targeting IGF2BP1 and Activating PI3K-Akt Signaling Pathway

Main Article Content

Ke Chen
Jia-Wei Chen
Yao Shen
Yun-Fei Wang
Sheng-Rong Dong
Xiao-Xue Zhang
Chen-Yang Li
Xiao-Juan Gao
Jia-Min Zhao
Yu-Nan Zhang
Wen-Ying Tian
Jia-Le Lv
Qiang Zhan
Fang-Mei An

Abstract

Background/Aims: The study focuses on examining the impact of Helicobacter pylori (H. pylori) on the modulation of the miRNA expression profiles while also unraveling the associated pathways that play a significant role in initiating and driving the development of gastric cancer (GC).


Materials and Methods: An in-depth analysis of miRNA expression profiles in gastric tissue samples from patients with chronic superficial gastritis (CSG), chronic atrophic gastritis (CAG), dysplasia (Dys), or GC was conducted. The carbon-13 urea breath test was used to identify H. pylori infection, and the participant cohort was characterized by the presence of H. pylori infection. Additionally, the role of miR-196a/b-5p in GC carcinogenesis was investigated.


Results: A total of five miRNAs—miR-196a-5p, 196b-5p, 224-5p, 424-3p, and 941—demonstrated marked elevation in CSG, CAG, Dys, and GC. miR-196a/b-5p was observed to be upregulated in GC cells following H. pylori infection, as well as in Dys and GC tissue samples from patients harboring H. pylori. miR-196a/b-5p can expedite GC progression. Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), the target gene of miR-196a/b-5p, diminishes the proliferation capability of GC cells; however, miR-196a/b-5p can partially counteract this effect. miR-196a/b-5p activates the PI3K-Akt pathway, while IGF2BP1 inhibits the expression of these proteins.


Conclusion: The levels of miR-196a/b-5p were observed to escalate following H. pylori infection, subsequently fostering the progression of GC by specifically targeting IGF2BP1 and triggering the PI3K-Akt signaling cascade.

Cite this article as: Chen K, Chen JW, Shen Y, et al. Helicobacter pylori promoted miR-196a/b-5p expression and accelerated tumorigenesis of the gastric mucosa by targeting IGF2BP1 and activating PI3K-Akt signaling pathway. Turk J Gastroenterol. Published online May 5, 2025. doi 10.5152/tjg.2025.24397.

Article Details

References

1. Van Cutsem E, Sagaert X, Topal B, et al. Gastric cancer. Lancet. 2016;388(10060):2654-2664. [CrossRef]

2. Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66(2):115-132. [CrossRef]

3. Ouyang J, Xie Z, Lei X, et al. Clinical crosstalk between microRNAs and GC. Int J Oncol. 2021;58(4):7. [CrossRef]

4. Hooi J, Lai WY, Ng WK, et al. Global prevalence of H. pylori infection: systematic review and meta-analysis. Gastroenterology. 2017;153(2):420-429. [CrossRef]

5. Choi IJ, Kook MC, Kim YI, et al. H. pylori therapy for the prevention of metachronous GC. N Engl J Med. 2018;378(12):1085-1095. [CrossRef]

6. Chen YC, Malfertheiner P, Yu HT, et al. Global prevalence of Helicobacter pylori infection and incidence of gastric cancer between 1980 and 2022. Gastroenterology. 2024;166(4):605-619. [CrossRef]

7. Lee JW, Kim N, Park JH, et al. Differential microRNA expression between gastric cancer tissue and non-cancerous gastric mucosa according to Helicobacter pylori status. J Cancer Prev. 2017;22(1):33-39. [CrossRef]

8. Xu HM, Huang K, Shi MX, et al. MicroRNAs in Helicobacter pylori-infected gastric cancer: function and clinical application. Pharmacol Res. 2024;205:107216. [CrossRef]

9. Plummer M, Franceschi S, Vignat J, et al. Global burden of GC attributable to Helicobacter pylori. Int J Cancer. 2015;136(2):487-490. [CrossRef]

10. Link A, Schirrmeister W, Langner C, et al. Differential expression of microRNAs in preneoplastic gastric mucosa. Sci Rep. 2015;5:8270. [CrossRef]

11. Tan X, Tang H, Bi J, et al. MicroRNA-222-3p associated with H. pylori targets HIPK2 to promote cell proliferation, invasion, and inhibits apoptosis in GC. J Cell Biochem. 2018;119(7):5153-5162. [CrossRef]

12. Zhou X, Xia Y, Li L, et al. MiR-101 inhibits cell growth and tumorigenesis of H. pylori-related GC by repression of SOCS2. Cancer Biol Ther. 2015;16(1):160-169. [CrossRef]

13. Hwang J, Min BH, Jang J, et al. MicroRNA expression profiles in gastric carcinogenesis. Sci Rep. 2018;8(1):14393. [CrossRef]

14. Shi Y, Wang Z, Zhu X, et al. Exosomal miR-1246 in serum as a potential biomarker for early diagnosis of GC. Int J Clin Oncol. 2020;25(1):89-99. [CrossRef]

15. Xiong M, Wang P, Pan B, et al. The diagnostic and prognostic values of microRNA-196a in cancer. Biosci Rep. 2021;41(1):BSR20203559. [CrossRef]

16. Li HL, Xie SP, Yang YL, et al. Clinical significance of upregulation of miR-196a-5p in GC and enriched KEGG pathway analysis of target genes. Asian Pac J Cancer Prev. 2015;16(5):1781-1787. [CrossRef]

17. Jin L, Ma XM, Wang TT, et al. Psoralen suppresses cisplatin-mediated resistance and induces apoptosis of gastric adenocarcinoma by disruption of the miR-196a–HOXB7–HER2 axis. Cancer Manag Res. 2020;12:2803-2827. [CrossRef]

18. Shao L, Chen Z, Peng D, et al. Methylation of the HOXA10 promoter directs miR-196b-5p-dependent cell proliferation and invasion of GC cells. Mol Cancer Res. 2018;16(4):696-706. [CrossRef]

19. Li J, Wang L, He F, et al. Long noncoding RNA LINC00629 restrains the progression of GC by upregulating AQP4 through competitively binding to miR-196b-5p. J Cell Physiol. 2020;235(3):2973-2985. [CrossRef]

20. Huang X, Zhang H, Guo X, et al. Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) in cancer. J Hematol Oncol. 2018;11(1):88. [CrossRef]

21. Yang DL, Dong LF, Qiu YB, et al. An oncogenic lncRNA, GLCC1, promotes tumorigenesis in gastric carcinoma by enhancing the c-Myc/IGF2BP1 interaction. Neoplasma. 2021;68(5):1052-1062. [CrossRef]

22. Wang X, Guan D, Wang D, et al. Genetic variants in m6A regulators are associated with GC risk. Arch Toxicol. 2021;95(3):1081-1088. [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.