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Updated: Oct 26, 2025
Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer
Published on: March 14, 2019
Hsa_circ_0136666 activates Treg-mediated immune escape of colorectal cancer via miR-497/PD-L1 pathway
Yan-Jie Xu1, Jie-Min Zhao1, Cao Gao2
1Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou 213000, Jiangsu Province, PR China.
Insights
Circular RNA hsa_circ_0136666 promotes colorectal cancer growth by increasing PD-L1 and activating Treg cells. This study reveals a new mechanism involving miR-497, offering a potential therapeutic strategy for colorectal cancer.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Colorectal cancer is a leading cause of cancer mortality and incidence globally.
- Circular RNA hsa_circ_0136666 (hsa_circ_0136666) is implicated in colorectal cancer progression.
- The precise mechanisms by which hsa_circ_0136666 influences colorectal cancer tumorigenesis require further elucidation.
Purpose of the Study:
- To investigate the role of hsa_circ_0136666 in colorectal cancer.
- To explore the involvement of hsa_circ_0136666 in aberrant regulatory T cell (Treg) activation and tumor immune evasion.
- To identify hsa_circ_0136666 as a potential therapeutic target for colorectal cancer treatment.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) and Western blotting to assess gene and protein expression.
- Dual-luciferase reporter and RNA immunoprecipitation assays to determine molecular interactions.
- Cell proliferation, apoptosis assays, and xenograft models to evaluate functional effects in vitro and in vivo.
Main Results:
- hsa_circ_0136666 and PD-L1 expression were elevated, while miR-497 levels were decreased in colorectal cancer tissues.
- hsa_circ_0136666 directly targets miR-497, which in turn regulates PD-L1 expression.
- hsa_circ_0136666 promotes cell proliferation, inhibits apoptosis, stimulates Treg cells via the miR-497/PD-L1 axis, and accelerates tumor growth in vivo.
Conclusions:
- hsa_circ_0136666 enhances colorectal cancer progression by upregulating PD-L1 through miR-497 inhibition.
- This mechanism leads to Treg cell activation and tumor immune escape, offering novel insights into colorectal cancer pathogenesis.
- Targeting hsa_circ_0136666 presents a promising therapeutic strategy for colorectal cancer.
Purpose:
In the rankings of cancer mortality and incidence worldwide, colorectal cancer ranks fourth and the third, respectively. Circular RNA hsa_circ_0136666 (hsa_circ_0136666) is reported to participate in the growth of colorectal cancer. However, the mechanism by which hsa_circ_0136666 regulates the tumorigenesis of colorectal cancer needs to be further explored. In this study, we report here the role of hsa_circ_0136666 in the aberrant activation of Treg cells and immune evasion of tumor cells, providing a new strategy for the treatment of colorectal cancer.
Methods:
Western blotting assay and qRT-PCR assay were used to determine protein and mRNA expression levels. Dual-luciferase reporter assay was used to evaluate the targeted regulatory relationship. RNA immunoprecipitation was used to detect RNA binding. Colony formation assay was utilized to measure the cell proliferation. Flow cytometry was used to assess cell apoptosis. Xenograft model was setup to evaluate tumor growth.
Results:
The results showed that hsa_circ_0136666 and PD-L1 was increased in colorectal cancer cells while miR-497 was decreased in colorectal cancer cells when compared with normal colon epithelial cell line. Hsa_circ_0136666 was demonstrated to directly target miR-497, which also regulated PD-L1 by binding to its 3'UTR. Further mechanistic studies identified that hsa_circ_0136666 controlled cell proliferation and apoptosis via targeting miR-497 and regulating PD-L1 expression. Of note, hsa_circ_0136666 stimulated Treg cells mediated by miR-497/PD-L1 axis and its downstream signal pathway in Treg cells. Finally, hsa_circ_0136666 was found to accelerate the tumor growth in vivo.
Conclusions:
Our findings demonstrated that hsa_circ_0136666 promoted the expression of PD-L1 by inhibiting miR-497 level in colorectal cancer, thus inducing the activation of Treg cells and leading to the immune escape of tumor, providing a novel mechanistic insight into the pathogenesis of colorectal cancer.
