Related Experiment Video
Updated: Aug 12, 2026
Evaluation of Tumor-infiltrating Leukocyte Subsets in a Subcutaneous Tumor Model
Published on: April 13, 2015
MLK4 as an immune marker and its correlation with immune infiltration in Cervical squamous cell carcinoma and
Meng Gong1, Fujin Shen1, Yang Li1
1Gynecology Department, Renmin Hospital of Wuhan University, Wuhan, China.
Abstract:
Mixed pedigree kinase 4 (MLK4) is a member of the serine/threonine kinases mixed pedigree kinase (MLKs) family. Few reports on immune-related targets in Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), and the role of MLK4 in cervical cancer remains to be studied. The expression of MLK4 in CESC was analyzed by TCGA database containing 306 CESC tissues and 3 peritumoral tissue samples, and the effect of MLK4 on immune invasion was evaluated using the Deseq2 package(Benjamini-Hochberg corrected p-value < 0.05 and log2 fold change ≥|2|). Tissue microarray was used to verify the expression of MLK4 in CESC patients, and it was found that MLK4 was significantly overexpressed in CESC, and significantly correlated with WHO grade. Multiple analysis algorithms revealed that the high expression of MLK4 was negatively correlated with immune cell infiltration in CESC. Analysis showed that MLK4 expression was negatively correlated with the infiltration of various immune cells including CD8+T cells, and MLK4 mRNA expression was positively correlated with immune checkpoints PD-L1,CTLA4, LAG3, and negatively correlated with immune promotion genes CD86 and CD80. Furthermore, vitro assays were performed to investigate the biological characteristics of MLK4 in C33A cells. The EDU and transwell assays demonstrated that the decrease in MLK4 expression in C33A cells resulted in a decrease in cell proliferation and invasion. The silencing of MLK4 resulted in a significant increase in the expression of inflammatory cytokines IL-1β(p<0.05), TNF-α(p<0.01), and IL-6 (p<0.05). The results of cell assays indicate that knocking down MLK4 would inhibit the expression of established biochemical markers CEA, AFP and HCG. Hence, it is plausible that MLK4 could potentially exert a significant influence on the development and progression of Cervical cancer.
Insights
Mixed lineage kinase 4 (MLK4) is overexpressed in cervical cancer and linked to reduced immune cell infiltration. Silencing MLK4 inhibits cancer cell proliferation and invasion, suggesting MLK4 as a potential therapeutic target in cervical cancer.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Mixed lineage kinase 4 (MLK4) is part of the serine/threonine kinases mixed lineage kinase (MLK) family.
- The role of MLK4 in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) and its association with immune responses are not well understood.
Purpose of the Study:
- To investigate the expression of MLK4 in CESC tissues.
- To evaluate the correlation between MLK4 expression and immune cell infiltration in CESC.
- To explore the functional role of MLK4 in CESC cell proliferation, invasion, and inflammatory responses.
Main Methods:
- Analysis of MLK4 expression in CESC using The Cancer Genome Atlas (TCGA) database and tissue microarrays.
- Evaluation of MLK4's effect on immune invasion using the Deseq2 package.
- In vitro assays (EDU, transwell) to assess the impact of MLK4 knockdown on C33A cell proliferation, invasion, and cytokine expression (IL-1β, TNF-α, IL-6).
Main Results:
- MLK4 was significantly overexpressed in CESC tissues and correlated with WHO grade.
- High MLK4 expression was negatively correlated with the infiltration of immune cells, including CD8+ T cells.
- MLK4 expression positively correlated with immune checkpoints (PD-L1, CTLA4, LAG3) and negatively with immune promotion genes (CD86, CD80).
- MLK4 knockdown reduced C33A cell proliferation and invasion, increased inflammatory cytokines, and inhibited tumor markers (CEA, AFP, HCG).
Conclusions:
- MLK4 is upregulated in CESC and associated with a suppressed immune microenvironment.
- MLK4 plays a role in promoting cervical cancer cell proliferation and invasion.
- MLK4 inhibition may represent a potential therapeutic strategy for cervical cancer.
More Related Videos
07:29Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
08:29Author Spotlight: Multiplex Immunohistochemistry for Understanding Immune Regulation by Uterine NK Cells in Pregnancy
Published on: October 25, 2024
