CCT3-LINC00326axis regulates hepatocarcinogenic lipid metabolism

Abstract

ObjectiveTo better comprehend transcriptional phenotypes of cancer cells, we globally characterised RNA-binding proteins (RBPs) to identify altered RNAs, including long non-coding RNAs (lncRNAs).DesignTo unravel RBP-lncRNA interactions in cancer, we curated a list of ~2300 highly expressed RBPs in human cells, tested effects of RBPs and lncRNAs on patient survival in multiple cohorts, altered expression levels, integrated various sequencing, molecular and cell-based data.ResultsHigh expression of RBPs negatively affected patient survival in 21 cancer types, especially hepatocellular carcinoma (HCC). After knockdown of the top 10 upregulated RBPs and subsequent transcriptome analysis, we identified 88 differentially expressed lncRNAs, including 34 novel transcripts. CRISPRa-mediated overexpression of four lncRNAs had major effects on the HCC cell phenotype and transcriptome. Further investigation of four RBP-lncRNA pairs revealed involvement in distinct regulatory processes. The most noticeable RBP-lncRNA connection affected lipid metabolism, whereby the non-canonical RBP CCT3 regulated LINC00326 in a chaperonin-independent manner. Perturbation of the CCT3-LINC00326 regulatory network led to decreased lipid accumulation and increased lipid degradation in cellulo as well as diminished tumour growth in vivo.ConclusionsWe revealed that RBP gene expression is perturbed in HCC and identified that RBPs exerted additional functions beyond their tasks under normal physiological conditions, which can be stimulated or intensified via lncRNAs and affected tumour growth.

Bioinformatics analysis and experimental verification of the prognostic and biological significance mediated by fatty acid metabolism related genes for hepatocellular carcinoma

“…Thus, it is extremely necessary to explore novel and efficient markers of diagnosis and prognosis for improving the OS of HCC patients ( 41 ). Increasing studies have shown that metabolic dysregulation is one of the main characteristics of malignant tumor cells, leading to growth, angiogenesis, proliferation, and invasion ( 42 – 44 ). FA metabolism, as an important part of energy metabolism, is involved in multiple biological processes for promoting tumorigenesis and progression ( 13 ).…”

HLA-DQB1-AS1 Promotes Cell Proliferation, Inhibits Apoptosis, and Binds with ZRANB2 Protein in Hepatocellular Carcinoma

“…HLA-DQB1 Block2 CCCCC haplotype confers beneficial effects in hepatitis B virus-related hepatocellular carcinoma patients after hepatic resection [ 22 ]. lncRNAs can interact with RNA binding proteins to regulate hepatocellular carcinoma [ 23 ]. A representative example is that uroplakin 1A antisense RNA 1 promotes cell proliferation in hepatocellular carcinoma through interaction with enhancer of zeste 2 polycomb repressive complex 2 subunit [ 24 ].…”

The role and mechanism of noncoding RNAs in regulation of metabolic reprogramming in hepatocellular carcinoma

“…On the one hand, HULC activated the ACSL1 promoter in HCC cells by upregulating the transcription factor PPARA; on the other hand, HULC induced methylation of CpG islands in the miR‐9 promoter to inhibit miR‐9 targeting of PPARA mRNA 141 . Additionally, a recent study identified that perturbation of the CCT3‐LINC00326 axis reduced lipid accumulation and increased lipid degradation in HCC cells, as well as diminished tumor growth in vivo 142 (Figure 2).…”