The RNA-Binding Protein NELFE Promotes Gastric Cancer Growth and Metastasis Through E2F2

Overview

Journal Front Oncol

Specialty Oncology

Date 2021 Jul 23

PMID 34295816

Citations 7

Authors

Changyu Chen

Qiang Zheng

Shubo Pan

Wenzheng Chen

Jianfeng Huang

Yi Cao

Yi Tu

Zhengrong Li

Changjun Yu

Zhigang Jie

Affiliations

Soon will be listed here.

Abstract

Worldwide, the incidence rate of gastric cancer ranks fifth, and the mortality rate of gastric cancer ranks third among all malignant tumors. However, the pathogenesis of gastric cancer remains poorly understood. In this study, we demonstrated that the expression level of NELFE is higher in human gastric cancer tissues than in adjacent nontumor tissues. A high level of NELFE is associated with worse postoperative overall survival (OS) and relapse-free survival (RFS) rates in patients with gastric cancer. Moreover, the expression of NELFE is correlated with high tumor grade and lymph node metastasis in gastric cancer patients. Knockdown of NELFE dramatically inhibits the cell proliferation and metastasis of gastric cancer xenografts . Furthermore, we found that NELFE binding to the 3'UTR of E2F2 affects the mRNA stability of E2F2 to regulate the expression level of E2F2. In gastric cancer, E2F2 also acts as an oncogene to inhibit the proliferation and migration of gastric cancer cells by knocking down the expression level of E2F2. However, overexpressing E2F2 in cells with NELFE knockdown significantly reverses the inhibition of cell proliferation and migration induced by NELFE knockdown. Therefore, NELFE at least partially functions as an oncogene through E2F2. Moreover, CIBERSORTx analysis of the proportion of tumor-infiltrating immune cells (TICs) revealed that immune cells are correlated with NELFE and E2F2 expression, suggesting that NELFE and E2F2 might be responsible for the preservation of the immunodominant status for gastric cancer. In conclusion, NELFE acts as an oncogene in gastric cancer and can be used as a potential therapeutic target.

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References

Borisova M, Voigt A, Tollenaere M, Sahu S, Juretschke T, Kreim N . p38-MK2 signaling axis regulates RNA metabolism after UV-light-induced DNA damage. Nat Commun. 2018; 9(1):1017. PMC: 5845016. DOI: 10.1038/s41467-018-03417-3. View

Liu X, Hu C . Novel Potential Therapeutic Target for E2F1 and Prognostic Factors of E2F1/2/3/5/7/8 in Human Gastric Cancer. Mol Ther Methods Clin Dev. 2020; 18:824-838. PMC: 7479313. DOI: 10.1016/j.omtm.2020.07.017. View

Bi K, Wei X, Qin X, Li B . BTK Has Potential to Be a Prognostic Factor for Lung Adenocarcinoma and an Indicator for Tumor Microenvironment Remodeling: A Study Based on TCGA Data Mining. Front Oncol. 2020; 10:424. PMC: 7175916. DOI: 10.3389/fonc.2020.00424. View

Guo Q, Wu Y, Guo X, Cao L, Xu F, Zhao H . The RNA-Binding Protein CELF2 Inhibits Ovarian Cancer Progression by Stabilizing FAM198B. Mol Ther Nucleic Acids. 2020; 23:169-184. PMC: 7734233. DOI: 10.1016/j.omtn.2020.10.011. View

Zhang Y, Wang Z, Ma J, Huo J, Li Y, Wang Y . Bioinformatics Identification of the Expression and Clinical Significance of E2F Family in Endometrial Cancer. Front Genet. 2020; 11:557188. PMC: 7672218. DOI: 10.3389/fgene.2020.557188. View

Wen L, Cheng F, Zhou Y, Yin C . MiR-26a enhances the sensitivity of gastric cancer cells to cisplatin by targeting NRAS and E2F2. Saudi J Gastroenterol. 2015; 21(5):313-9. PMC: 4632257. DOI: 10.4103/1319-3767.166206. View

Joshi S, Badgwell B . Current treatment and recent progress in gastric cancer. CA Cancer J Clin. 2021; 71(3):264-279. PMC: 9927927. DOI: 10.3322/caac.21657. View

Sun C, Li S, Hu W, Zhang J, Zhou Q, Liu C . RETRACTED: Comprehensive Analysis of the Expression and Prognosis for E2Fs in Human Breast Cancer. Mol Ther. 2019; 27(6):1153-1165. PMC: 6554685. DOI: 10.1016/j.ymthe.2019.03.019. View

Dang H, Takai A, Forgues M, Pomyen Y, Mou H, Xue W . Oncogenic Activation of the RNA Binding Protein NELFE and MYC Signaling in Hepatocellular Carcinoma. Cancer Cell. 2017; 32(1):101-114.e8. PMC: 5539779. DOI: 10.1016/j.ccell.2017.06.002. View

10.

Manicum T, Ni F, Ye Y, Fan X, Chen B . Prognostic values of mRNA expression in human gastric cancer. Biosci Rep. 2018; 38(6). PMC: 6435564. DOI: 10.1042/BSR20181264. View

11.

Sakurai T, Isogaya K, Sakai S, Morikawa M, Morishita Y, Ehata S . RNA-binding motif protein 47 inhibits Nrf2 activity to suppress tumor growth in lung adenocarcinoma. Oncogene. 2016; 35(38):5000-9. PMC: 5036161. DOI: 10.1038/onc.2016.35. View

12.

Yu S, Li L, Cai H, He B, Gao Y, Li Y . Overexpression of NELFE contributes to gastric cancer progression via Wnt/β-catenin signaling-mediated activation of CSNK2B expression. J Exp Clin Cancer Res. 2021; 40(1):54. PMC: 7851912. DOI: 10.1186/s13046-021-01848-3. View

13.

Jiang Y, Xie J, Huang W, Chen H, Xi S, Han Z . Tumor Immune Microenvironment and Chemosensitivity Signature for Predicting Response to Chemotherapy in Gastric Cancer. Cancer Immunol Res. 2019; 7(12):2065-2073. DOI: 10.1158/2326-6066.CIR-19-0311. View

14.

Yu J, Fang C, Zhang Z, Zhang G, Shi L, Qian J . Rises in Gastric Cancer and Exerts a Tumor-Promoting Function via / Axis. Cancer Manag Res. 2020; 12:13033-13042. PMC: 7762430. DOI: 10.2147/CMAR.S267357. View

15.

Naudin C, Hattabi A, Michelet F, Miri-Nezhad A, Benyoucef A, Pflumio F . PUMILIO/FOXP1 signaling drives expansion of hematopoietic stem/progenitor and leukemia cells. Blood. 2017; 129(18):2493-2506. PMC: 5429137. DOI: 10.1182/blood-2016-10-747436. View

16.

Sung H, Ferlay J, Siegel R, Laversanne M, Soerjomataram I, Jemal A . 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. DOI: 10.3322/caac.21660. View

17.

Yang T, Sahu D, Chang Y, Hsu C, Hsieh C, Huang H . RNA-Binding Proteomics Reveals MATR3 Interacting with lncRNA SNHG1 To Enhance Neuroblastoma Progression. J Proteome Res. 2018; 18(1):406-416. DOI: 10.1021/acs.jproteome.8b00693. View

18.

Cosker K, Fenstermacher S, Pazyra-Murphy M, Elliott H, Segal R . The RNA-binding protein SFPQ orchestrates an RNA regulon to promote axon viability. Nat Neurosci. 2016; 19(5):690-696. PMC: 5505173. DOI: 10.1038/nn.4280. View

19.

Han W, Xin Z, Zhao Z, Bao W, Lin X, Yin B . RNA-binding protein PCBP2 modulates glioma growth by regulating FHL3. J Clin Invest. 2013; 123(5):2103-18. PMC: 3635714. DOI: 10.1172/JCI61820. View

20.

Yu H, Li Z, Wang M . Expression and prognostic role of E2F transcription factors in high-grade glioma. CNS Neurosci Ther. 2020; 26(7):741-753. PMC: 7299000. DOI: 10.1111/cns.13295. View