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Updated: Mar 7, 2026
Development of Compendium for Esophageal Squamous Cell Carcinoma
Published on: April 12, 2024
MiR-498 in esophageal squamous cell carcinoma: clinicopathological impacts and functional interactions
Farhadul Islam1, Vinod Gopalan2, Simon Law3
1Cancer Molecular Pathology of School of Medicine and Menzies Health Institute Queensland, Griffith University, Gold Coast, 4222, Australia; Department of Biochemistry and Molecular Biology, University of Rajshahi, 6205, Bangladesh.
Abstract:
MicroRNA-498 plays a crucial role in progression of many carcinomas. The signaling pathways by which miR-498 modulates carcinogenesis are still unknown. Also, miR-498-associated molecular pathogenesis has never been studied in esophageal squamous cell carcinoma (ESCC). Herein, we aimed to examine the expression and functional roles of miR-498 in ESCC as well as its influences on the clinicopathological features in patients with ESCC. Expression of miR-498 was investigated in 93 ESCC tissues and 5 ESCC cell lines using quantitative real-time polymerase chain reaction. In vitro effects of miR-498 on cellular process were studied followed by overexpression of miR-498. Western blot and immunofluorescence techniques were used to identify the interacting targets for miR-498 in ESCC. miR-498 expression was significantly reduced in ESCC when compared with the nonneoplastic esophageal tissues (P<.05). Patients with low miR-498 expression showed different histological grading of cancer and survival rates when compared with the patients with high miR-498 expression. Overexpression of miR-498 in ESCC cell lines induced remarkable reductions of cell proliferation, barrier penetration, and colony formation when compared with control and wild-type counterparts. Also, miR-498 activated the FOXO1/KLF6 transcriptional axis in ESCC. In addition, miR-498 overexpression increased p21 protein expression and led to reduced cancer cell growth. To conclude, reduced expression of miR-498 in ESCC and in vitro analysis have confirmed the tumor suppressor properties of miR-498 by modulating the FOXO1/KLF6 signaling pathway. The changes in miR-498 expression may have impacts on the clinical pathological parameters of ESCC as well as in the management of the patients with ESCC.
Insights
MicroRNA-498 (miR-498) acts as a tumor suppressor in esophageal squamous cell carcinoma (ESCC). Reduced miR-498 expression correlates with poor prognosis, and its restoration inhibits ESCC progression by modulating the FOXO1/KLF6 pathway.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNA-498 (miR-498) is implicated in various carcinomas, but its role in esophageal squamous cell carcinoma (ESCC) remains unelucidated.
- The molecular pathogenesis and signaling pathways influenced by miR-498 in ESCC are not well understood.
Purpose of the Study:
- To investigate the expression patterns of miR-498 in ESCC tissues and cell lines.
- To determine the functional role of miR-498 in ESCC progression and its impact on clinicopathological features.
- To identify the molecular targets and signaling pathways modulated by miR-498 in ESCC.
Main Methods:
- Quantitative real-time polymerase chain reaction (qRT-PCR) to assess miR-498 expression in 93 ESCC tissues and 5 cell lines.
- In vitro experiments involving miR-498 overexpression in ESCC cell lines to evaluate effects on proliferation, invasion, and colony formation.
- Western blot and immunofluorescence assays to identify miR-498 interacting targets and confirm activation of the FOXO1/KLF6 pathway and p21 expression.
Main Results:
- miR-498 expression was significantly downregulated in ESCC tissues compared to non-neoplastic controls.
- Low miR-498 expression was associated with poorer histological grading and survival rates in ESCC patients.
- Overexpression of miR-498 suppressed ESCC cell proliferation, invasion, and colony formation in vitro.
- miR-498 activated the FOXO1/KLF6 transcriptional axis and increased p21 protein expression, leading to reduced cancer cell growth.
Conclusions:
- Reduced miR-498 expression is a characteristic feature of ESCC and confers tumor suppressor properties.
- miR-498 modulates ESCC progression through the FOXO1/KLF6 signaling pathway and influences p21 expression.
- Aberrant miR-498 expression may serve as a prognostic biomarker and therapeutic target in ESCC management.
