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Interaction between MALAT-1, CCR7 and correlated genes in oral squamous cell carcinoma
Zixiao Xu1, Xu Han1, Zhen Tang1
1Department of Stomatology, Changhai Hospital Affiliated to The Second Military Medical University Shanghai, China.
Objective:
This study focuses on the feasible molecular mechanism of the interaction between MALAT-1, CCR7 and related genes in oral squamous cell carcinoma, to find new target molecules that can block the lymph node metastasis.
Methods:
The expression of MALAT-1, miRNA-320s, SRSF1, YB-1 and CCR7 were detected in T3/T4-phase OSCC tissues of two groups with or without lymph node metastasis using real-time qPCR. CO-IP and western blot to test the interaction of RNAs (MALAT-1, miRNA-320s) with SRSF1 protein or YB-1 were evaluated by CO-IP, Western blot and real-time qPCR. The expression change of chemokine receptor CCR7 were investigated using CO-IP, Western blot and real-time qPCR after silencing miRNA-320d (one of the miRNA-320s family members) by transfection of miRNA mimics to explore related signaling pathway.
Results:
The expression levels of MALAT-1 SRSF1 and CCR7 in OSCC tissues with were differentially higher compared with those of samples without lymph node metastasis as well as para-carcinoma tissues, exclusive of miRNA-320d. Moreover, it is confirmed that the target RNA (MALAT-1, miRNA-320s) and SRSF1 protein can combine with each other, based on the statistically significant difference compared with negative control group (P<0.05). In addition, the expression of CCR7 was higher than the negative control group after silencing miRNA-320d.
Conclusion:
SRSF1 is likely to mediate the interactive relationship between MALAT-1 and miRNA-320d. CCR7 expression can be distinctly increased by silencing miRNA-320d. The effect of long-chain non-coding RNA MALAT-1 on chemokine receptor CCR7 and possibly further influence on lymph node metastasis of oral squamous cell carcinoma are revealed in molecular level to offer help for prevention and treatment of OSCC in future.
Insights
This study reveals how MALAT-1, SRSF1, and miRNA-320d interact to influence chemokine receptor CCR7 expression in oral squamous cell carcinoma (OSCC). Understanding this mechanism may help block lymph node metastasis in OSCC patients.
Area of Science:
- Molecular Biology
- Oncology
- Gene Regulation
Background:
- Oral squamous cell carcinoma (OSCC) is a prevalent cancer where lymph node metastasis significantly impacts prognosis.
- Identifying molecular mechanisms driving metastasis is crucial for developing targeted therapies.
- Long non-coding RNAs (lncRNAs) like MALAT-1 are increasingly implicated in cancer progression.
Purpose of the Study:
- To elucidate the molecular interactions between MALAT-1, CCR7, and associated genes in OSCC.
- To identify potential molecular targets for inhibiting lymph node metastasis in OSCC.
- To explore the role of SRSF1 and miRNA-320d in regulating CCR7 expression.
Main Methods:
- Real-time quantitative PCR (qPCR) to measure expression levels of MALAT-1, miRNA-320s, SRSF1, YB-1, and CCR7 in OSCC tissues.
- Co-immunoprecipitation (CO-IP) and Western blot assays to confirm interactions between RNA molecules and SRSF1/YB-1 proteins.
- Transfection of miRNA mimics to silence miRNA-320d and assess its effect on CCR7 expression and signaling pathways.
Main Results:
- Elevated expression of MALAT-1, SRSF1, and CCR7 was observed in OSCC tissues with lymph node metastasis compared to those without and adjacent normal tissues.
- Direct interaction between MALAT-1, miRNA-320s, and SRSF1 protein was confirmed.
- Silencing of miRNA-320d led to a significant increase in CCR7 expression.
Conclusions:
- SRSF1 acts as a mediator in the interaction between MALAT-1 and miRNA-320d.
- miRNA-320d plays a role in regulating CCR7 expression, with its silencing increasing CCR7 levels.
- This research sheds light on the molecular underpinnings of MALAT-1's influence on CCR7 and its potential role in OSCC lymph node metastasis, offering therapeutic targets.
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