LncRNA CRNDE facilitates epigenetic suppression of CELF2 and LATS2 to promote proliferation, migration and chemoresistance in hepatocellular carcinoma

Abstract

Our study aimed to investigate the expression, functional significance, and related mechanism of long noncoding RNA CRNDE (colorectal neoplasia differentially expressed) in hepatocellular carcinoma (HCC) pathogenesis. The resulted revealed that CRNDE was significantly overexpressed in HCC tissues and cell lines, and was statistically correlated with poor clinical outcome. CRNDE knockdown markedly decreased HCC cell proliferation, migration, and chemoresistance. In addition, in vivo experiments confirmed the suppressive effect of CRNDE knockdown on HCC progression. Mechanically, CRNDE directly bound to EZH2 (enhancer of zeste homolog), SUZ12 (suppressor of zeste 12), SUV39H1, and mediated their inhibition of tumor suppressor genes, including CUGBP Elav-like family member 2 (CELF2) and large tumor suppressor 2 (LATS2). CELF2 exerted tumor suppressive effect in HCC and was involved in CRNDE-mediated oncogenic effect. In addition, the oncogenic effects of CRNDE on HCC proliferation, migration and tumorigenesis, as well as its inhibition of Hippo pathway were abolished by LATS2 overexpression. Together, our work demonstrated the importance of CRNDE in HCC progression and elucidated the underlying molecular mechanisms. These findings provided new insights into HCC pathogenesis and chemoresistance mediated by CRNDE.

Integrated Transcriptional Profiling Analysis and Immune-Related Risk Model Construction for Intracranial Aneurysm Rupture

“…We obtained ceRNA networks with 8 DElncRNAs, 13 DEmiRNAs, and 19 DEmRNAs. CRANDE plays a role in tumor proliferation, migration, and the occurrence of many other diseases ( Zhou et al, 2019a ; Xie et al, 2020 ). CRANDE interacts with TLR3, and both correlate with advanced disease inflammation in sepsis patients ( Yang et al, 2020 ).…”

Pan-cancer characterization of long non-coding RNA and DNA methylation mediated transcriptional dysregulation

“…7e, logrank test P=0.012). CRNDE has been identified to interact with PRC2 component EZH2 and mediated their inhibition of tumor suppressor genes [68]. Elevated expression and the associated poor prognosis was found in many cancer types, including pancreatic cancer [69,70].…”

Regulation of Metabolic Reprogramming by Long Non-Coding RNAs in Cancer

“…Interestingly, recent evidence suggests that lncRNAs might also contribute to the development of drug resistance in various cancers, either by modulating drug metabolism or by altering key signaling pathways and cellular processes, leading to drug efflux, enhanced DNA damage repair, cell cycle alterations or resistance to apoptosis [ 62 ]. In cervical cancer, for example, MALAT1 overexpression promotes the development of cisplatin resistance via the PI3K/AKT signaling pathway [ 63 ], while in hepatocellular carcinoma (HCC), the long noncoding RNA CRNDE (colorectal neoplasia differentially expressed) has been correlated with poor clinical outcome and chemoresistance by inhibiting the tumor suppressor genes CUGBP Elav-like family member 2 (CELF2) and large tumor suppressor 2 (LATS2) [ 64 ].…”