Exploring the mechanism of LncRNA CASC15 affecting hepatocellular carcinoma through miRNA

Author:

Cai Qingshan1,Wu Dongyang1,Shen Yueling2,Li Shudong1,Liu Liyou1,Liu Dong1,Li Yong3,Chen Xiaonan4,Wang Limin1,Zheng Jianxing1ORCID

Affiliation:

1. Department of Hepatobiliary Surgery, Tangshan Central Hospital, Hebei Province, China

2. Department of Otolaryngology, Qian ‘an People’s Hospital, Hebei Province, China

3. Department of General Surgery, Tangshan Eighth Hospital, Hebei Province, China

4. Hepatobiliary Surgery Department, Tangshan Gongren Hospital, Hebei Province, China.

Abstract

This study aimed to determine the potential mechanisms through which long noncoding (Lnc) RNA cancer susceptibility candidate 15 (CASC15) affects hepatocellular carcinoma (HCC). We retrieved HCC RNA-seq and clinical information from the UCSC Xena database. The differential expression (DE) of CASC15 was detected. Overall survival was analyzed using Kaplan–Meier (K–M) curves. Molecular function and signaling pathways affected by CASC15 were determined using Gene Set Enrichment Analysis. Associations between CASC15 and the HCC microenvironment were investigated using immuno-infiltration assays. A differential CASC15-miRNA-mRNA network and HCC-specific CASC15-miRNA-mRNA ceRNA network were constructed. The overexpression of CASC15 in HCC tissues was associated with histological grade, clinical stage, pathological T stage, poor survival, more complex immune cell components, and 12 immune checkpoints. We identified 27 DE miRNAs and 270 DE mRNAs in the differential CASC15-miRNA-mRNA network, and 10 key genes that were enriched in 12 cancer-related signaling pathways. Extraction of the HCC-specific CASC15-miRNA-mRNA network revealed that IGF1R, MET, and KRAS were associated with HCC progression and occurrence. Our bioinformatic findings confirmed that CASC15 is a promising prognostic biomarker for HCC, and elevated levels in HCC are associated with the tumor microenvironment. We also constructed a disease-specific CASC15-miRNA-mRNA regulatory ceRNA network that provides a new perspective for the precise indexing of patients with elevated levels of CASC15.

Publisher

Ovid Technologies (Wolters Kluwer Health)

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