JoVE - Journal of Visualized Experiments
JoVE Visualize
Contact Us

TMB Signature-Related RCAN2 Promotes Apoptosis by Upregulating EHF/DR5 Pathway in Hepatocellular Carcinoma

  • 0Department of Hepatobiliary Pancreatic Surgery, Guangzhou First People's Hospital, 510000 Guangzhou, Guangdong, China.
Frontiers in Bioscience (landmark Edition) +

|

July 31, 2024

|

July 31, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

RCAN2 downregulation correlates with high tumor mutation burden (TMB) in cancers. In hepatocellular carcinoma (HCC), increased RCAN2 promotes apoptosis via the EHF/DR5 pathway, offering new treatment strategies.

Area Of Science

  • Oncology
  • Genomics
  • Molecular Biology

Background

  • Tumor mutation burden (TMB) is linked to tumor behavior and prognosis, but underlying genetic mechanisms remain unclear.
  • Identifying genes associated with TMB is crucial for understanding tumor biology and developing targeted therapies.

Purpose Of The Study

  • To identify key genes associated with TMB in hepatocellular carcinoma (HCC).
  • To investigate the biological functions, downstream factors, and mechanisms of TMB-related genes in HCC.

Main Methods

  • Analysis of The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) database to classify patients by TMB signature-related genes.
  • Identification of key prognostic genes using immunohistochemistry and qPCR.
  • In vitro and in vivo studies to assess the impact of gene expression on cell proliferation and apoptosis.
  • Utilizing databases and sequencing data to elucidate mechanisms and downstream transcription factors.

Main Results

  • A TMB signature-related gene group (IC2) showed significantly different TMB scores and better prognosis.
  • Five key prognostic genes were identified, with RCAN2 negatively correlated with TMB in 18 tumor types.
  • High RCAN2 expression correlated with better HCC survival, enhanced apoptosis, and involved the EHF/DR5 pathway.

Conclusions

  • RCAN2 downregulation is associated with elevated TMB across multiple cancer types.
  • RCAN2 serves as a prognostic biomarker in HCC and promotes apoptosis through the EHF/DR5 pathway.
  • These findings offer novel insights for systemic treatment of advanced HCC with high TMB.

Keywords:

Related Concept Videos

The Extrinsic Apoptotic Pathway 01:17

6.3K

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...

The Intrinsic Apoptotic Pathway 01:31

6.4K

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...

MAPK Signaling Cascades 01:07

5.3K

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...

Regulation of Angiogenesis and Blood Supply 01:24

2.5K

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...

Interactions Between Signaling Pathways 01:19

6.2K

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal 01:22

2.2K

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.