MRPL21 promotes HCC proliferation through TP53 mutation-induced apoptotic resistance
Tao Ma1, Ya-Bin Huang2, Jing Chen1
1Department of Gastroenterology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, China; Research Center of Clinical Medicine, Nantong University, Affiliated Hospital of Nantong University, Nantong, China.
Background And Aims:
The specific mechanisms underlying the inhibition of hepatocellular carcinoma (HCC) proliferation and metastasis by mitochondrial apoptosis are not yet fully understood. However, it plays a vital role in suppressing HCC's ability to proliferate and spread. The involvement of MRPL21, a member within the family of mitochondrial ribosomal proteins (MRPs), is well-documented in both cellular apoptosis and energy metabolism. This study aims to explore and unravel the underlying mechanisms through which MRPL21 contributes to mitochondrial apoptosis and resistance against apoptosis in HCC.
Methods:
To evaluate the level of MRPL21 expression at the gene and protein expression levels, analysis was performed on human liver samples and blood using techniques for quantification. A knockdown plasmid targeting MRPL21 was constructed to investigate its impact on the growth and apoptosis of hepatocellular carcinoma (HCC). To evaluate the impact of MRPL21 knockdown on hepatocellular carcinoma (HCC) cell proliferation and apoptosis, various assays were performed including CCK-8 assays, flow cytometry analysis, detection of reactive oxygen species (ROS), and assessment of mitochondrial membrane potential (MMP). Furthermore, the role of MRPL21 in TP53 mutation was examined using Nutlin-3.
Results:
In HCC tissues and blood samples, an upregulation of MRPL21 expression was observed when compared to samples obtained from healthy individuals, and it is correlated with a poor prognosis for HCC. Silencing MRPL21 can effectively suppress Hep3B and HCCLM3 cells proliferation by modulating the mitochondrial membrane potential, it triggers the generation of reactive oxygen species (ROS), thereby leading to G0/G1 cell cycle arrest and initiation of early apoptosis. Furthermore, by inhibiting P53 activity, Nutlin-3 treatment can enhance MRPL21-deficiency-mediated apoptosis in Hep3B and HCCLM3 cells.
Conclusion:
Through its influence on TP53 mutation, MRPL21 promotes HCC proliferation and progression while conferring resistance to apoptosis. These findings suggest that MRPL21 holds promise as a valuable biomarker for the treatment of HCC.
Insights
Mitochondrial ribosomal protein L21 (MRPL21) promotes hepatocellular carcinoma (HCC) growth and survival. Silencing MRPL21 induces apoptosis and cell cycle arrest, suggesting MRPL21 as a potential therapeutic target for HCC treatment.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Biology
Background:
- Mitochondrial apoptosis plays a role in suppressing hepatocellular carcinoma (HCC) proliferation and metastasis.
- Mitochondrial ribosomal protein L21 (MRPL21) is involved in cellular apoptosis and energy metabolism.
- The precise mechanisms by which MRPL21 influences HCC apoptosis remain unclear.
Purpose of the Study:
- To investigate the role of MRPL21 in HCC proliferation and apoptosis.
- To elucidate the mechanisms underlying MRPL21's contribution to mitochondrial apoptosis resistance in HCC.
- To explore the relationship between MRPL21, TP53 mutation, and HCC progression.
Main Methods:
- MRPL21 expression was quantified in HCC tissues and blood samples.
- MRPL21 was knocked down using a plasmid to assess its effects on HCC cell lines (Hep3B, HCCLM3).
- Cell proliferation, apoptosis, reactive oxygen species (ROS) levels, and mitochondrial membrane potential (MMP) were analyzed. The impact of TP53 inhibition on MRPL21-deficient cells was evaluated using Nutlin-3.
Main Results:
- MRPL21 expression was upregulated in HCC tissues and blood, correlating with poor prognosis.
- MRPL21 knockdown suppressed HCC cell proliferation by inducing G0/G1 cell cycle arrest and apoptosis.
- MRPL21 silencing modulated MMP, increased ROS generation, and enhanced apoptosis, particularly when combined with TP53 inhibition.
Conclusions:
- MRPL21 promotes HCC proliferation and progression by influencing TP53 mutation and conferring apoptosis resistance.
- MRPL21 is a potential therapeutic target for HCC treatment.
- MRPL21 may serve as a valuable biomarker for HCC treatment strategies.
More Related Videos
19:44Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen
Published on: May 30, 2012
06:51Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
Published on: July 21, 2018
Related Concept Videos
02:23Abnormal Proliferation
03:03mTOR Signaling and Cancer Progression
The mTOR pathway or the...
01:22PI3K/mTOR/AKT Signaling Pathway
01:19Interactions Between Signaling Pathways
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...
01:31The Intrinsic Apoptotic Pathway
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...