Activating Transcription Factor 3 is a New Biomarker Correlation with Renal Clear Cell Carcinoma Progression

Overview

Journal Int J Immunopathol Pharmacol

Publisher Sage Publications

Specialties Allergy & Immunology
Pathology
Pharmacology

Date 2024 Jan 22

PMID 38248871

Authors

Zhicong Yang

Yongwang Hou

Jingqi Li

Dandan Xu

Zhichao Yang

Xinsheng Wang

Affiliations

Soon will be listed here.

Abstract

Clear cell renal cell carcinoma (ccRCC) is the most invasive type of cancer, with a high risk of metastasis and recurrence. Therefore, there is an urgent need to identify novel prognostic predictors and therapeutic targets of ccRCC. Activating transcription factor 3 (ATF3), a tumor oncogene or repressor, has rarely been examined in ccRCC. In the present study, we comprehensively elucidate the prognostic value and potential functions of ATF3 in ccRCC. Several TCGA-based online databases were used to analyze ATF3 expression in ccRCC and determine ccRCC prognosis. The upstream-binding micro (mi) RNAs of ATF3 and long non-coding (lnc)RNAs were predicted using the StarBase database. Analysis of several TCGA-based online databases showed that ATF3 expression is decreased in ccRCC, suggesting a significant association with the prognosis of patients with ccRCC. Furthermore, we found hsa-miR-221-3p to be potential regulatory miRNA of ATF3 in ccRCC. Prediction and analysis of the upstream lncRNAs indicated that PAXIP1-AS2 and OIP5-AS1 were the most potent upstream lncRNAs of the hsa-miR-221-3p/ATF3 axis in ccRCC. The results of the GO and KEGG analyses implied that ATF3 is likely involved in the regulation of apoptotic signaling in response to endoplasmic reticulum (ER) stress in ccRCC. Correlation analysis revealed a positive relationship between ATF3 expression and ER stress. Our in silico findings highlighted that ATF3 expression was low in ccRCC and negatively correlated with poor prognosis. Furthermore, PAXIP1-AS2 and the OIP5-AS1/hsa-miR-221-3p/ATF3 axis were identified as significant potential regulators of ER stress-mediated apoptosis in ccRCC.

Citing Articles

The Cellular Stress and Cutaneous Manifestations in Renal Cell Carcinomas-A Narrative Review.

Ene C, Nicolae I, Tampa M, Georgescu S, Ene C, Matei C J Clin Med. 2024; 13(13).

PMID: 38999207 PMC: 11242689. DOI: 10.3390/jcm13133640.

References

Yan Q, Liu L, Yang H, Xu C, Wang Z, Wang Q . Long Non-Coding RNA OIP5-AS1 Inhibits the Proliferation and Migration of Esophageal Squamous Carcinoma Cells by Targeting FOXD1/miR-30a-5p Axis and the Effect of Micro- and Nano-Particles on Targeting Transfection System. J Biomed Nanotechnol. 2021; 17(7):1380-1391. DOI: 10.1166/jbn.2021.3114. View

Hou Y, Xiang B, Yang Z, Liu J, Xu D, Geng L . Down-regulation of interleukin-2 predicts poor prognosis and associated with immune escape in lung adenocarcinoma. Int J Immunopathol Pharmacol. 2023; 37:3946320231202748. PMC: 10515527. DOI: 10.1177/03946320231202748. View

Santoni M, Massari F, Bracarda S, Grande E, Matrana M, Rizzo M . Cabozantinib in Patients with Advanced Renal Cell Carcinoma Primary Refractory to First-line Immunocombinations or Tyrosine Kinase Inhibitors. Eur Urol Focus. 2022; 8(6):1696-1702. DOI: 10.1016/j.euf.2022.02.004. View

Quhal F, Mori K, Bruchbacher A, Resch I, Mostafaei H, Pradere B . First-line Immunotherapy-based Combinations for Metastatic Renal Cell Carcinoma: A Systematic Review and Network Meta-analysis. Eur Urol Oncol. 2021; 4(5):755-765. DOI: 10.1016/j.euo.2021.03.001. View

Wu L, Liu Y, Guo C, Shao Y . LncRNA OIP5-AS1 promotes the malignancy of pancreatic ductal adenocarcinoma via regulating miR-429/FOXD1/ERK pathway. Cancer Cell Int. 2020; 20:296. PMC: 7346488. DOI: 10.1186/s12935-020-01366-w. View

Amankwah E, Anegbe E, Park H, Pow-Sang J, Hakam A, Park J . miR-21, miR-221 and miR-222 expression and prostate cancer recurrence among obese and non-obese cases. Asian J Androl. 2013; 15(2):226-30. PMC: 3705740. DOI: 10.1038/aja.2012.160. View

de Sousa Valente J, Alawi K, Keringer P, Bharde S, Ayaz F, Saleque N . Examining the role of transient receptor potential canonical 5 (TRPC5) in osteoarthritis. Osteoarthr Cartil Open. 2020; 2(4):100119. PMC: 7762818. DOI: 10.1016/j.ocarto.2020.100119. View

Dvorska D, Brany D, nachajova M, Halasova E, Dankova Z . Breast Cancer and the Other Non-Coding RNAs. Int J Mol Sci. 2021; 22(6). PMC: 8005115. DOI: 10.3390/ijms22063280. View

Shi Z, Zhang K, Chen T, Zhang Y, Du X, Zhao Y . Transcriptional factor ATF3 promotes liver fibrosis via activating hepatic stellate cells. Cell Death Dis. 2020; 11(12):1066. PMC: 7734065. DOI: 10.1038/s41419-020-03271-6. View

10.

Sarhadi V, Armengol G . Molecular Biomarkers in Cancer. Biomolecules. 2022; 12(8). PMC: 9331210. DOI: 10.3390/biom12081021. View

11.

Hu Z, Lu Y, Cui D, Ma C, Shao S, Chen P . MicroRNAs and long non-coding RNAs in liver surgery: Diagnostic and therapeutic merits. Hepatobiliary Pancreat Dis Int. 2020; 19(3):218-228. DOI: 10.1016/j.hbpd.2020.04.002. View

12.

Liu G, Su L, Hao X, Zhong N, Zhong D, Singhal S . Salermide up-regulates death receptor 5 expression through the ATF4-ATF3-CHOP axis and leads to apoptosis in human cancer cells. J Cell Mol Med. 2011; 16(7):1618-28. PMC: 3823229. DOI: 10.1111/j.1582-4934.2011.01401.x. View

13.

Weaver C, Bin Satter K, Richardson K, Tran L, Tran P, Purohit S . Diagnostic and Prognostic Biomarkers in Renal Clear Cell Carcinoma. Biomedicines. 2022; 10(11). PMC: 9687861. DOI: 10.3390/biomedicines10112953. View

14.

Hou J, Huang Q, Fan Z, Sang H, Wu S, Cheng S . LncRNA OIP5-AS1 Knockdown Facilitated the Ferroptosis and Immune Evasion by Modulating the GPX4 in Oesophageal Carcinoma. Comput Math Methods Med. 2022; 2022:8103198. PMC: 9307385. DOI: 10.1155/2022/8103198. View

15.

Tian H, Chou F, Tian J, Zhang Y, You B, Huang C . ASC-J9® suppresses prostate cancer cell proliferation and invasion via altering the ATF3-PTK2 signaling. J Exp Clin Cancer Res. 2021; 40(1):3. PMC: 7780640. DOI: 10.1186/s13046-020-01760-2. View

16.

Rosellini M, Marchetti A, Mollica V, Rizzo A, Santoni M, Massari F . Prognostic and predictive biomarkers for immunotherapy in advanced renal cell carcinoma. Nat Rev Urol. 2022; 20(3):133-157. DOI: 10.1038/s41585-022-00676-0. View

17.

Wang Y, Chen D, Xie H, Jia M, Sun X, Peng F . AUF1 protects against ferroptosis to alleviate sepsis-induced acute lung injury by regulating NRF2 and ATF3. Cell Mol Life Sci. 2022; 79(5):228. PMC: 11072094. DOI: 10.1007/s00018-022-04248-8. View

18.

Santoni M, Rizzo A, Mollica V, Matrana M, Rosellini M, Faloppi L . The impact of gender on The efficacy of immune checkpoint inhibitors in cancer patients: The MOUSEION-01 study. Crit Rev Oncol Hematol. 2022; 170:103596. DOI: 10.1016/j.critrevonc.2022.103596. View

19.

Qiu B, Ackerman D, Sanchez D, Li B, Ochocki J, Grazioli A . HIF2α-Dependent Lipid Storage Promotes Endoplasmic Reticulum Homeostasis in Clear-Cell Renal Cell Carcinoma. Cancer Discov. 2015; 5(6):652-67. PMC: 4456212. DOI: 10.1158/2159-8290.CD-14-1507. View

20.

Yoo K, Kim D, Oh S, Park M, Kim H, Ha H . Transcriptome analysis upon potassium usnate exposure reveals ATF3-induced apoptosis in human gastric and colon cancer cells. Phytomedicine. 2021; 91:153655. DOI: 10.1016/j.phymed.2021.153655. View