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LncRNA GAS5 Suppresses Colorectal Cancer Progress by Target miR-21/LIFR Axis
Juan Xie1, Jing-Jing Wang1, Ya-Jun Li1
1Department of Gastroenterology, General Hospital of Ningxia Medical University, Ningxia 750004, Yinchuan, China.
Abstract:
GAS5 is abnormally high in colorectal cancer tissues, which is a specific expression of lncRNA in colorectal cancer (CRC). Nevertheless, its biological function in CRC has not been elucidated. The abnormal high expression of GAS5 in CRC is the specific expression of lncRNA in CRC. The purpose of our study is to explore the effect of GAS5 on CRC and its mechanism. The expression of GAS5 in 53 paired normal and colorectal cancer tissues and colorectal cancer cell lines was detected by real-time PCR. The biological effects of GAS5, miR-21, and LIFR were measured by functional assays, including wound healing, transwell assays, and in vivo assays. We ensured the carcinogenesis role of GAS5 in CRC in the xenograft nude model. The dual-luciferase reporter assay system and chromatin immunoprecipitation method were used for target evaluation and Western blot for verification. GAS5 was significantly decreased in tumor tissues and CRC cells, and the low expression of CAS5 in CRC promoted tumor metastasis and decreased the survival of patients. GAS5 knockdown increases the cell viability, inhibits apoptosis, and promotes migration. Xenografted tumors in nude mice studies showed that GAS5 knockdown promoted tumor growth and caused worse lesions in colorectal. Furthermore, GAS5 increases the expression level of target gene LIFR to promote the apoptosis of CRC cells by binding to miR-21. Our study revealed that a novel pathway about lncRNA GAS5 inhibited the proliferation and metastasis of CRC cells by targeting miR-21/LIFR which provides a new strategy to treat CRC.
Insights
Long non-coding RNA GAS5 is downregulated in colorectal cancer (CRC), promoting tumor growth and metastasis. Restoring GAS5 inhibits CRC progression by targeting the miR-21/LIFR pathway, offering a potential new treatment strategy.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Colorectal cancer (CRC) is a significant global health concern.
- Long non-coding RNAs (lncRNAs) play crucial roles in cancer development.
- The specific function of GAS5 in CRC remains largely unelucidated.
Purpose of the Study:
- To investigate the role and mechanism of GAS5 in colorectal cancer.
- To explore GAS5's potential as a therapeutic target for CRC.
Main Methods:
- Quantitative real-time PCR to assess GAS5 expression in patient tissues and cell lines.
- Functional assays (wound healing, Transwell, in vivo xenograft models) to evaluate GAS5's biological effects.
- Dual-luciferase reporter assays, chromatin immunoprecipitation, and Western blotting to elucidate the molecular mechanism involving miR-21 and LIFR.
Main Results:
- GAS5 expression was significantly decreased in colorectal cancer tissues and cells compared to normal tissues.
- GAS5 knockdown promoted CRC cell proliferation, migration, and inhibited apoptosis.
- In vivo studies demonstrated that GAS5 knockdown accelerated tumor growth and worsened lesions.
- GAS5 was found to target miR-21, upregulating LIFR expression and promoting CRC cell apoptosis.
Conclusions:
- GAS5 acts as a tumor suppressor in colorectal cancer.
- The lncRNA GAS5 inhibits CRC proliferation and metastasis via the miR-21/LIFR pathway.
- Targeting the GAS5/miR-21/LIFR axis presents a novel therapeutic strategy for CRC treatment.
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