Bioinformatics Analysis and Validation of the Role of Lnc-RAB11B-AS1 in the Development and Prognosis of Hepatocellular Carcinoma

Wang, Dedong; Hu, Xiangzhi; Chen, Jinbin; Liang, Boheng; Zhang, Lin; Qin, Pengzhe; Wu, Di

doi:10.3390/cells11213517

Cited by 4 publications

(2 citation statements)

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“…However, these metabolic enzymes did not harbor a canonical RNA-binding domain for CHKB-DT according to the online databases. 31,32 In contrast, FUS, a classic RBP recognizing characteristic RNA motifs in CHKB-DT, was most likely to be a key player of CHKB-DT mediated the phenotypic changes in the heart. Besides, ALDH2 overexpression completely rescued CHKB-DT knockdown–induced cardiac dysfunction, it appeared that CHKB-DT–mediated phenotypic changes in cardiac performance were ALDH2 dependent.…”

Section: Discussionmentioning

confidence: 98%

LncRNA CHKB-DT Downregulation Enhances Dilated Cardiomyopathy Through ALDH2

Nie,

Fan,

Dai

et al. 2024

Circulation Research

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Background: Human cardiac long noncoding RNA (lncRNA) profiles in patients with dilated cardiomyopathy (DCM) were previously analyzed, and the long noncoding RNA CHKB (choline kinase beta) divergent transcript (CHKB-DT) levels were found to be mostly downregulated in the heart. In this study, the function of CHKB-DT in DCM was determined. Methods: Long noncoding RNA expression levels in the human heart tissues were measured via quantitative reverse transcription–polymerase chain reaction and in situ hybridization assays. A CHKB-DT heterozygous or homozygous knockout mouse model was generated using the clustered regularly interspaced palindromic repeat (CRISPR)/CRISPR-associated protein 9 system, and the adeno-associated virus with a cardiac-specific promoter was used to deliver the RNA in vivo. Sarcomere shortening was performed to assess the primary cardiomyocyte contractility. The Seahorse XF cell mitochondrial stress test was performed to determine the energy metabolism and ATP production. Furthermore, the underlying mechanisms were explored using quantitative proteomics, ribosome profiling, RNA antisense purification assays, mass spectrometry, RNA pull-down, luciferase assay, RNA–fluorescence in situ hybridization, and Western blotting. Results: CHKB-DT levels were remarkably decreased in patients with DCM and mice with transverse aortic constriction–induced heart failure. Heterozygous knockout of CHKB-DT in cardiomyocytes caused cardiac dilation and dysfunction and reduced the contractility of primary cardiomyocytes. Moreover, CHKB-DT heterozygous knockout impaired mitochondrial function and decreased ATP production as well as cardiac energy metabolism. Mechanistically, ALDH2 (aldehyde dehydrogenase 2) was a direct target of CHKB-DT. CHKB-DT physically interacted with the mRNA of ALDH2 and FUS (RNA-binding protein FUS) through the GGUG motif. CHKB-DT knockdown aggravated ALDH2 mRNA degradation and 4-hydroxy-2-nonenal production, whereas overexpression of CHKB-DT reversed these molecular changes. Furthermore, restoring ALDH2 expression in CHKB-DT +/ − mice alleviated cardiac dilation and dysfunction. Conclusions: CHKB-DT is significantly downregulated in DCM. CHKB-DT acts as an energy metabolism-associated long noncoding RNA and represents a promising therapeutic target against DCM.

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Section: Discussionmentioning

confidence: 98%

LncRNA CHKB-DT Downregulation Enhances Dilated Cardiomyopathy Through ALDH2

Nie,

Fan,

Dai

et al. 2024

Circulation Research

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“…Low expression of lnc-RAB11B-AS1 was associated with shorter OS and DFS in HCC patients. The high expression of RAB11B reduced PD-L1 expression, thereby inhibiting the progression of HCC ( 152 ). LncRNA AC099850.3 was up-regulated in HCC tissues, and its high expression was associated with poor prognosis in HCC patients.…”

Section: Expression Of Pd-l1 In Tumor Cellsmentioning

confidence: 99%

The current status and future of PD-L1 in liver cancer

Hao,

Li,

Deng

et al. 2023

Front. Immunol.

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The application of immunotherapy in tumor, especially immune checkpoint inhibitors (ICIs), has played an important role in the treatment of advanced unresectable liver cancer. However, the efficacy of ICIs varies greatly among different patients, which has aroused people’s attention to the regulatory mechanism of programmed death ligand-1 (PD-L1) in the immune escape of liver cancer. PD-L1 is regulated by multiple levels and signaling pathways in hepatocellular carcinoma (HCC), including gene variation, epigenetic inheritance, transcriptional regulation, post-transcriptional regulation, and post-translational modification. More studies have also found that the high expression of PD-L1 may be the main factor affecting the immunotherapy of liver cancer. However, what is the difference of PD-L1 expressed by different types of cells in the microenvironment of HCC, and which type of cells expressed PD-L1 determines the effect of tumor immunotherapy remains unclear. Therefore, clarifying the regulatory mechanism of PD-L1 in liver cancer can provide more basis for liver cancer immunotherapy and combined immune treatment strategy. In addition to its well-known role in immune regulation, PD-L1 also plays a role in regulating cancer cell proliferation and promoting drug resistance of tumor cells, which will be reviewed in this paper. In addition, we also summarized the natural products and drugs that regulated the expression of PD-L1 in HCC.

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