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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
Downregulation of microRNA-498 in colorectal cancers and its cellular effects
Vinod Gopalan1, Robert A Smith1, Alfred K-Y Lam1
1Cancer Molecular Pathology, School of Medicine and Griffith Health Institute, Griffith University, Gold Coast, QLD, Australia.
Abstract:
miR-498 is a non-coding RNA located intergenically in 19q13.41. Due to its predicted targeting of several genes involved in control of cellular growth, we examined the expression of miR-498 in colon cancer cell lines and a large cohort of patients with colorectal adenocarcinoma. Two colon cancer cancer cell lines (SW480 and SW48) and one normal colonic epithelial cell line (FHC) were recruited. The expression of miR-498 was tested in these cell lines by using quantitative real-time polymerase chain reaction (qRT-PCR). Tissues from 80 patients with surgical resection of colorectum (60 adenocarcinomas and 20 non-neoplastic tissues) were tested for miR-498 expression by qRT-PCR. In addition, an exogenous miR-498 (mimic) was used to detect the miRNA׳s effects on cell proliferation and cell cycle events in SW480 using MTT calorimetric assay and flow cytometry respectively. The colon cancer cell lines showed reduced expression of miR-498 compared to a normal colonic epithelial cell line. Mimic driven over expression of miR-498 in the SW480 cell line resulted in reduced cell proliferation and increased proportions of G2-M phase cells. In tissues, miR-498 expression was too low to be detected in all colorectal adenocarcinoma compared to non-neoplastic tissues. This suggests that the down regulation of miR-498 in colorectal cancer tissues and the direct suppressive cellular effect noted in cancer cell lines implies that miR-498 has some direct or indirect role in the pathogenesis of colorectal adenocarcinomas.
Insights
MicroRNA-498 (miR-498) shows reduced expression in colorectal cancer, suppressing cell proliferation and impacting the cell cycle. This suggests miR-498 plays a role in colorectal adenocarcinoma development.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- MicroRNA-498 (miR-498) is a non-coding RNA implicated in cellular growth regulation.
- Its role in colorectal cancer pathogenesis requires further investigation.
Purpose of the Study:
- To investigate the expression levels of miR-498 in colorectal cancer cell lines and patient tissues.
- To determine the functional impact of miR-498 on colorectal cancer cell proliferation and cell cycle progression.
Main Methods:
- Quantitative real-time polymerase chain reaction (qRT-PCR) was used to assess miR-498 expression in cell lines and patient tissues.
- MTT assay and flow cytometry were employed to evaluate the effects of miR-498 overexpression on SW480 cell proliferation and cell cycle.
- Analysis included two colon cancer cell lines, one normal colonic epithelial cell line, and tissues from 80 patients (60 adenocarcinomas, 20 non-neoplastic).
Main Results:
- Colon cancer cell lines exhibited significantly lower miR-498 expression compared to normal colonic epithelial cells.
- Overexpression of miR-498 in SW480 cells led to decreased cell proliferation and an increased proportion of cells in the G2-M phase.
- miR-498 expression was undetectable in all colorectal adenocarcinoma tissues analyzed, contrasting with non-neoplastic tissues.
Conclusions:
- Downregulation of miR-498 is a characteristic feature of colorectal adenocarcinoma.
- The observed suppressive effects of miR-498 on cancer cell proliferation and cell cycle suggest its role as a tumor suppressor in colorectal cancer.
- These findings indicate that miR-498 may be involved in the pathogenesis of colorectal adenocarcinomas.
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