The LncRNA CRNDE is Regulated by E2F6 and Sensitizes Gastric Cancer Cells to Chemotherapy by Inhibiting Autophagy

Overview

Journal J Cancer

Specialty Oncology

Date 2022 Sep 1

PMID 36046639

Authors

Feifei Zhang

Qian Chen

Peng Chen

Chaoqun Liu

Hui Wang

Liang Zhao

Affiliations

Soon will be listed here.

Abstract

Chemotherapy is an important treatment for gastric cancer (GC), but the primary and secondary drug resistance of tumours to chemotherapy seriously affects its curative effect. In recent years, the relationship between long noncoding RNAs (lncRNAs) and malignant tumours has received increasing attention. Based on accumulating evidence, lncRNAs are involved in the chemoresistance of GC, but the underlying mechanisms remain unclear. In this study, we identified the lncRNA colorectal neoplasia differentially expressed (CRNDE) as an important regulator of autophagy-associated chemoresistance in GC. Mechanistically, overexpression of CRNDE inhibits autophagy and induces apoptosis, thereby sensitizing GC cells to chemotherapy drugs. Moreover, E2F6, a classical transcriptional inhibitor, is confirmed to be upregulated in GC and represses the expression of CRNDE. The E2F6-CRNDE axis is clinically related to chemoresistant GC and poor outcomes in patients with advanced GC. Our findings suggest that the E2F6-CRNDE axis is a viable therapeutic target to protect against chemoresistance in GC.

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References

Wang K, Chang H . Molecular mechanisms of long noncoding RNAs. Mol Cell. 2011; 43(6):904-14. PMC: 3199020. DOI: 10.1016/j.molcel.2011.08.018. View

Liu Z, Bi X, Liu P, Lei D, Wang Y, Li Z . Expressions and prognostic values of the transcription factors in human breast carcinoma. Cancer Manag Res. 2018; 10:3521-3532. PMC: 6145639. DOI: 10.2147/CMAR.S172332. View

Jing H, Xia H, Qian M, Lv X . Long noncoding RNA CRNDE promotes non-small cell lung cancer progression via sponging microRNA-338-3p. Biomed Pharmacother. 2018; 110:825-833. DOI: 10.1016/j.biopha.2018.12.024. View

Zhu L, Yang N, Du G, Li C, Liu G, Liu S . LncRNA CRNDE promotes the epithelial-mesenchymal transition of hepatocellular carcinoma cells via enhancing the Wnt/β-catenin signaling pathway. J Cell Biochem. 2018; 120(2):1156-1164. PMC: 6587876. DOI: 10.1002/jcb.26762. View

Chen M, Zhuang C, Liu Y, Li J, Dai F, Xia M . Tetracycline-inducible shRNA targeting antisense long non-coding RNA HIF1A-AS2 represses the malignant phenotypes of bladder cancer. Cancer Lett. 2016; 376(1):155-64. DOI: 10.1016/j.canlet.2016.03.037. View

Corazzari M, Rapino F, Ciccosanti F, Giglio P, Antonioli M, Conti B . Oncogenic BRAF induces chronic ER stress condition resulting in increased basal autophagy and apoptotic resistance of cutaneous melanoma. Cell Death Differ. 2014; 22(6):946-58. PMC: 4423179. DOI: 10.1038/cdd.2014.183. 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

Zheng J, Liu X, Wang P, Xue Y, Ma J, Qu C . CRNDE Promotes Malignant Progression of Glioma by Attenuating miR-384/PIWIL4/STAT3 Axis. Mol Ther. 2016; 24(7):1199-1215. PMC: 5088760. DOI: 10.1038/mt.2016.71. View

Zhang X, Liu H, Chen S . Mechanisms of Long Non-Coding RNAs in Cancers and Their Dynamic Regulations. Cancers (Basel). 2020; 12(5). PMC: 7281179. DOI: 10.3390/cancers12051245. View

10.

Han S, Han B, Li Z, Sun D . Downregulation of long noncoding RNA CRNDE suppresses drug resistance of liver cancer cells by increasing microRNA-33a expression and decreasing HMGA2 expression. Cell Cycle. 2019; 18(19):2524-2537. PMC: 6738913. DOI: 10.1080/15384101.2019.1652035. View

11.

Graham L, Pedersen S, Brown G, Ho T, Kassir Z, Moynihan A . Colorectal Neoplasia Differentially Expressed (CRNDE), a Novel Gene with Elevated Expression in Colorectal Adenomas and Adenocarcinomas. Genes Cancer. 2012; 2(8):829-40. PMC: 3278902. DOI: 10.1177/1947601911431081. View

12.

Cottone L, Capobianco A, Gualteroni C, Perrotta C, Bianchi M, Rovere-Querini P . 5-Fluorouracil causes leukocytes attraction in the peritoneal cavity by activating autophagy and HMGB1 release in colon carcinoma cells. Int J Cancer. 2014; 136(6):1381-9. DOI: 10.1002/ijc.29125. View

13.

Zhang Q, Sun M, Zhou S, Guo B . Class I HDAC inhibitor mocetinostat induces apoptosis by activation of miR-31 expression and suppression of E2F6. Cell Death Discov. 2016; 2:16036. PMC: 4979414. DOI: 10.1038/cddiscovery.2016.36. View

14.

Li Y, Lei Y, Yao N, Wang C, Hu N, Ye W . Autophagy and multidrug resistance in cancer. Chin J Cancer. 2017; 36(1):52. PMC: 5482965. DOI: 10.1186/s40880-017-0219-2. View

15.

Chen M, Li J, Zhuang C, Cai Z . Increased lncRNA ABHD11-AS1 represses the malignant phenotypes of bladder cancer. Oncotarget. 2017; 8(17):28176-28186. PMC: 5438641. DOI: 10.18632/oncotarget.14945. View

16.

Galluzzi L, Bravo-San Pedro J, Levine B, Green D, Kroemer G . Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles. Nat Rev Drug Discov. 2017; 16(7):487-511. PMC: 5713640. DOI: 10.1038/nrd.2017.22. View

17.

Ravikumar B, Sarkar S, Davies J, Futter M, Garcia-Arencibia M, Green-Thompson Z . Regulation of mammalian autophagy in physiology and pathophysiology. Physiol Rev. 2010; 90(4):1383-435. DOI: 10.1152/physrev.00030.2009. View

18.

Yu B, Ye X, Du Q, Zhu B, Zhai Q, Li X . The Long Non-Coding RNA CRNDE Promotes Colorectal Carcinoma Progression by Competitively Binding miR-217 with TCF7L2 and Enhancing the Wnt/β-Catenin Signaling Pathway. Cell Physiol Biochem. 2017; 41(6):2489-2502. DOI: 10.1159/000475941. View

19.

Han P, Li J, Zhang B, Lv J, Li Y, Gu X . The lncRNA CRNDE promotes colorectal cancer cell proliferation and chemoresistance via miR-181a-5p-mediated regulation of Wnt/β-catenin signaling. Mol Cancer. 2017; 16(1):9. PMC: 5237133. DOI: 10.1186/s12943-017-0583-1. View

20.

Korourian A, Madjd Z, Roudi R, Shariftabrizi A, Soleimani M . Induction of miR-31 causes increased sensitivity to 5-FU and decreased migration and cell invasion in gastric adenocarcinoma. Bratisl Lek Listy. 2019; 120(1):35-39. DOI: 10.4149/BLL_2019_005. View