The CircRNA CircSCAF8 Promotes Tumor Growth and Metastasis of Gastric Cancer Via MiR-1293/TIMP1signaling

Overview

Journal Gene Ther

Date 2024 Oct 28

PMID 39465333

Authors

Bin Mei

Jiajie Chen

Yang Peng

Affiliations

Soon will be listed here.

Abstract

SR-like CTD-associated factor 8 (SCAF8) can regulate transcriptional termination, but the function of circSCAF8 remains unclear. In our study, we observed a significant increase in circSCAF8 expression in gastric cancer, particularly in tissues with lymph node metastasis. The Kaplan-Meier curve revealed that high circSCAF8 expression was associated with a low overall survival time in gastric cancer patients. Moreover, circSCAF8 shRNA effectively decreased gastric cancer proliferation, invasion, and migration in vitro. Additionally, using bioluminescence imaging (BLI) technology in vivo, we found that circSCAF8 shRNA viruses inhibited the growth of xenograft tumors and gastric cancer lung metastasis. RNA immunoprecipitation (RIP) and circRNA pulldown assays confirmed the direct binding of circSCAF8 to miR-1293, but circSCAF8 could not regulate the expression of miR-1293 in gastric cancer. Interestingly, circSCAF8 regulated the downstream gene tissue inhibitor of metalloproteinases 1 (TIMP1) of miR-1293, and this observation was further verified in gastric cancer tissues. Moreover, we confirmed that miR-1293 directly suppressed TIMP1 expression. Subsequent rescue experiments revealed that TIMP1 overexpression reversed the impact of circSCAF8 shRNA viruses on gastric cancer. In conclusion, circSCAF8 expression was elevated in gastric cancer, and circSCAF8 shRNA viruses inhibited gastric cancer growth and metastasis by upregulating TIMP1 expression via miR-1293.

References

Sexton R, Al Hallak M, Diab M, Azmi A . Gastric cancer: a comprehensive review of current and future treatment strategies. Cancer Metastasis Rev. 2020; 39(4):1179-1203. PMC: 7680370. DOI: 10.1007/s10555-020-09925-3. View

Wong M, Huang J, Chan P, Choi P, Lao X, Chan S . Global Incidence and Mortality of Gastric Cancer, 1980-2018. JAMA Netw Open. 2021; 4(7):e2118457. PMC: 8314143. DOI: 10.1001/jamanetworkopen.2021.18457. View

Yuan L, Xu Z, Ruan S, Mo S, Qin J, Cheng X . Long non-coding RNAs towards precision medicine in gastric cancer: early diagnosis, treatment, and drug resistance. Mol Cancer. 2020; 19(1):96. PMC: 7251695. DOI: 10.1186/s12943-020-01219-0. View

Li Y, Feng A, Zheng S, Chen C, Lyu J . Recent Estimates and Predictions of 5-Year Survival in Patients with Gastric Cancer: A Model-Based Period Analysis. Cancer Control. 2022; 29:10732748221099227. PMC: 9067041. DOI: 10.1177/10732748221099227. View

Thrumurthy S, Chaudry M, Hochhauser D, Mughal M . The diagnosis and management of gastric cancer. BMJ. 2013; 347:f6367. DOI: 10.1136/bmj.f6367. View

Collatuzzo G, Pelucchi C, Negri E, Lopez-Carrillo L, Tsugane S, Hidaka A . Exploring the interactions between Helicobacter pylori (Hp) infection and other risk factors of gastric cancer: A pooled analysis in the Stomach cancer Pooling (StoP) Project. Int J Cancer. 2021; 149(6):1228-1238. DOI: 10.1002/ijc.33678. View

Liu T, Zhu J, Du W, Ning W, Zhang Y, Zeng Y . AKT2 drives cancer progression and is negatively modulated by miR-124 in human lung adenocarcinoma. Respir Res. 2020; 21(1):227. PMC: 7466426. DOI: 10.1186/s12931-020-01491-0. View

Miliotis C, Slack F . miR-105-5p regulates PD-L1 expression and tumor immunogenicity in gastric cancer. Cancer Lett. 2021; 518:115-126. PMC: 8355212. DOI: 10.1016/j.canlet.2021.05.037. View

Zhou T, Lin K, Nie J, Pan B, He B, Pan Y . LncRNA SPINT1-AS1 promotes breast cancer proliferation and metastasis by sponging let-7 a/b/i-5p. Pathol Res Pract. 2020; 217:153268. DOI: 10.1016/j.prp.2020.153268. View

10.

Dong R, Ma X, Chen L, Yang L . Increased complexity of circRNA expression during species evolution. RNA Biol. 2016; 14(8):1064-1074. PMC: 5680680. DOI: 10.1080/15476286.2016.1269999. View

11.

Jiang H, Tian Y, Zhao X, Zhang L, Wu Z . A circular RNA derived from FAT atypical cadherin 3 promotes lung cancer progression via forming a regulatory loop with oncogenic ELAV like RNA binding protein 1. J Biochem. 2021; 171(5):519-528. DOI: 10.1093/jb/mvab107. View

12.

Rybak-Wolf A, Stottmeister C, Glazar P, Jens M, Pino N, Giusti S . Circular RNAs in the Mammalian Brain Are Highly Abundant, Conserved, and Dynamically Expressed. Mol Cell. 2015; 58(5):870-85. DOI: 10.1016/j.molcel.2015.03.027. View

13.

Hou L, Zhang J . Circular RNAs: An emerging type of RNA in cancer. Int J Immunopathol Pharmacol. 2017; 30(1):1-6. PMC: 5806781. DOI: 10.1177/0394632016686985. View

14.

Zhu C, Sha X, Wang Y, Li J, Zhang M, Guo Z . Circular RNA hsa_circ_0007142 Is Upregulated and Targets miR-103a-2-5p in Colorectal Cancer. J Oncol. 2019; 2019:9836819. PMC: 6617873. DOI: 10.1155/2019/9836819. View

15.

Wang R, Zhang S, Chen X, Li N, Li J, Jia R . CircNT5E Acts as a Sponge of miR-422a to Promote Glioblastoma Tumorigenesis. Cancer Res. 2018; 78(17):4812-4825. DOI: 10.1158/0008-5472.CAN-18-0532. View

16.

Chen N, Zhao G, Yan X, Lv Z, Yin H, Zhang S . A novel FLI1 exonic circular RNA promotes metastasis in breast cancer by coordinately regulating TET1 and DNMT1. Genome Biol. 2018; 19(1):218. PMC: 6290540. DOI: 10.1186/s13059-018-1594-y. View

17.

Lou J, Hao Y, Lin K, Lyu Y, Chen M, Wang H . Circular RNA CDR1as disrupts the p53/MDM2 complex to inhibit Gliomagenesis. Mol Cancer. 2020; 19(1):138. PMC: 7487905. DOI: 10.1186/s12943-020-01253-y. View

18.

Yang H, Li X, Meng Q, Sun H, Wu S, Hu W . CircPTK2 (hsa_circ_0005273) as a novel therapeutic target for metastatic colorectal cancer. Mol Cancer. 2020; 19(1):13. PMC: 6977296. DOI: 10.1186/s12943-020-1139-3. View

19.

Liang H, Zhang X, Liu B, Jia G, Li W . Circular RNA circ-ABCB10 promotes breast cancer proliferation and progression through sponging miR-1271. Am J Cancer Res. 2017; 7(7):1566-1576. PMC: 5523036. View

20.

Li J, Chen K, Dong X, Xu Y, Sun Q, Wang H . YTHDF1 promotes mRNA degradation via YTHDF1-AGO2 interaction and phase separation. Cell Prolif. 2021; 55(1):e13157. PMC: 8780909. DOI: 10.1111/cpr.13157. View