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Published on: October 10, 2017
Ectopic expression of miR-944 impairs colorectal cancer cell proliferation and invasion by targeting GATA binding
Jing-Tong Tang1, Jinbo Zhao1, Weiwei Sheng1
1Department of Gastrointestinal Surgery & Hernia and Abdominal Wall Surgery, The First Hospital, China Medical University, Shenyang, Liaoning, China.
Abstract:
miR-944 is a microRNA that has been reported to play different important roles in the progression of cancer. Colorectal cancer (CRC) is a common cancer worldwide. A recent study has confirmed that miR-944 plays a tumour suppressive role in CRC. However, biological functions and the mechanism of miR-944 in CRC are poorly understood. Real-time reverse transcription polymerase chain reaction of 100 CRC tissues showed that miR-944 expression is frequently downregulated and is negatively associated with the T is the primary tumor, N is the lymph node, and M is the distant metastasis (TNM) stage (P = 0.009), depth of invasion (P = 0.001), and lymph node status (P = 0.002). Overexpression of mir-944 significantly impaired the functions of proliferation, migration and invasion in CRC cells, while these functions increased in knockdown experiments. GATA binding protein 6 (GATA6) knockdown can reverse the CRC cells functions induced by miR-944 inhibitor. Mechanistically, a Dual-Luciferase Reporter Assay showed that miR-944 is structurally combined with GATA6 and interacts with downstream proteins (CRT and p-AKT) in CRC cells. In conclusion, these findings indicated that miR-944 may be a tumour suppressor and could likely be used as a prognostic predictor and novel therapeutic target for CRC.
Insights
MicroRNA-944 acts as a tumor suppressor in colorectal cancer (CRC) by inhibiting proliferation and metastasis. Its downregulation correlates with advanced CRC stages, suggesting potential as a prognostic marker.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Colorectal cancer (CRC) is a significant global health concern.
- MicroRNA-944 (miR-944) has emerging roles in cancer progression.
- The specific functions and mechanisms of miR-944 in CRC remain largely undefined.
Purpose of the Study:
- To investigate the role of miR-944 in colorectal cancer.
- To elucidate the underlying molecular mechanisms of miR-944 in CRC.
- To assess the potential of miR-944 as a prognostic biomarker and therapeutic target for CRC.
Main Methods:
- Real-time reverse transcription polymerase chain reaction (RT-PCR) was used to quantify miR-944 expression in 100 CRC tissues.
- In vitro experiments assessed the effects of miR-944 overexpression and knockdown on CRC cell proliferation, migration, and invasion.
- GATA binding protein 6 (GATA6) knockdown and Dual-Luciferase Reporter Assays were employed to explore the interaction between miR-944 and GATA6.
Main Results:
- miR-944 expression was frequently downregulated in CRC tissues and negatively correlated with TNM stage, invasion depth, and lymph node status.
- Overexpression of miR-944 suppressed CRC cell proliferation, migration, and invasion, while knockdown enhanced these functions.
- miR-944 directly targets GATA6, influencing downstream proteins CRT and p-AKT, and GATA6 knockdown reversed miR-944 inhibitor-induced CRC cell changes.
Conclusions:
- miR-944 functions as a tumor suppressor in colorectal cancer.
- miR-944 exhibits potential as a prognostic predictor for CRC.
- miR-944 represents a promising novel therapeutic target for colorectal cancer treatment.
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