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MiR-183 functions as an oncogene by targeting ABCA1 in colon cancer
Da-Peng Bi1, Cheng-Hua Yin1, Xiao-Yue Zhang1
1The Second Department of Internal Medicine, Jinan Second People's Hospital, Jinan, Shandong 250001, P.R. China.
Abstract:
Colon cancer remains the second most common cause of cancer-related death, indicating that a proportion of cancer cells are not eradicated by current therapies. Investigation of the molecular mechanisms involved in the development and progression of the disease will aid in the further understanding of the pathogenesis and progression and offer new targets for effective therapies. In the present study, we initially confirmed that ABCA1 was aberrantly expressed in colon cancer tissues and colon cancer cells. Its overexpression inhibited the proliferation of colon cancer HCT116 cells while silencing of ABCA1 promoted the proliferation and inhibited the apoptosis of colon cancer LDL1 cells. Upregulation of specific miRNAs can contribute to the downregulation of tumor-suppressive genes. Thus, we aimed to ascertain whether ABCA1 is downregulated by overexpression of a specific miRNA in colon cancer. We screened microRNAs that may target ABCA1 by miRanda which is a commonly used prediction algorithm. We found that miR-183 targets the 3'UTR of ABCA1 mRNA. Subsequent experiments confirmed that miR-183 degraded ABCA1 mRNA in the colon cancer cells. Finally, we demonstrated that miR-183 promoted the proliferation and inhibited the apoptosis of colon cancer cells. Thus, we conclude that miR-183 promotes proliferation and inhibits apoptosis by degrading ABCA1 in colon cancer.
Insights
Colon cancer progression is linked to aberrant ABCA1 expression. MicroRNA-183 (miR-183) promotes colon cancer growth by downregulating ABCA1, inhibiting apoptosis.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Colon cancer is a leading cause of cancer mortality, with current therapies failing to eradicate all cancer cells.
- Understanding the molecular mechanisms driving colon cancer pathogenesis is crucial for developing effective therapeutic strategies.
- Aberrant expression of ATP-binding cassette transporter A1 (ABCA1) has been observed in colon cancer tissues.
Purpose of the Study:
- To investigate the role of ABCA1 in colon cancer proliferation and apoptosis.
- To identify microRNAs (miRNAs) that regulate ABCA1 expression in colon cancer.
- To elucidate the functional impact of miR-183 on colon cancer cell behavior.
Main Methods:
- Confirmation of ABCA1 aberrant expression in colon cancer.
- Assessment of ABCA1's effect on colon cancer cell proliferation and apoptosis (HCT116 and LDL1 cell lines).
- Bioinformatic prediction (miRanda) and experimental validation of miRNA targeting ABCA1 mRNA.
- Analysis of miR-183's impact on colon cancer cell proliferation and apoptosis.
Main Results:
- ABCA1 overexpression inhibited colon cancer cell proliferation, while ABCA1 silencing promoted proliferation and inhibited apoptosis.
- miR-183 was identified as a miRNA targeting the 3'UTR of ABCA1 mRNA.
- miR-183 was confirmed to degrade ABCA1 mRNA in colon cancer cells.
- miR-183 overexpression promoted colon cancer cell proliferation and inhibited apoptosis.
Conclusions:
- ABCA1 plays a tumor-suppressive role in colon cancer.
- miR-183 acts as an oncogenic miRNA in colon cancer by downregulating ABCA1.
- The miR-183/ABCA1 axis represents a potential therapeutic target for colon cancer treatment.
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