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Downregulated ARID1A by miR-185 Is Associated With Poor Prognosis and Adverse Outcomes in Colon Adenocarcinoma
- Source :
- Frontiers in Oncology, Vol 11 (2021), Frontiers in Oncology
- Publication Year :
- 2021
- Publisher :
- Frontiers Media S.A., 2021.
-
Abstract
- AT-rich interaction domain 1A (ARID1A) is a tumor suppressor gene that mutates in several cancer types, including breast cancer, ovarian cancer, and colorectal cancer (CRC). In colon adenocarcinoma (COAD), the low expression of ARID1A was reported but the molecular reason is unclear. We noticed that ARID1A low expression was associated with increased levels of miR-185 in the COAD. Therefore, this study aims to explore ncRNA-dependent mechanism that regulates ARID1A expression in COAD regarding miR-185. The expression of ARID1A was tested in COAD cell line under the effect of miR-185 mimics compared with inhibitor. The molecular features associated with loss of ARID1A and its association with tumor prognosis were analyzed using multi-platform data from The Cancer Genome Atlas (TCGA), and gene set enrichment analysis (GSEA) to identify potential signaling pathways associated with ARID1A alterations in colon cancer. Kaplan-Meier survival curve showed that a low level of ARID1A was closely related to low survival rate in patients with COAD. Results showed that inhibiting miR-185 expression in the COAD cell line significantly restored the expression of ARID1A. Further, the increased expression of ARID1A significantly improved the prolonged overall survival of COAD. We noticed that there is a possible relationship between ARID1A high expression and tumor microenvironment infiltrating immune cells. Furthermore, the increase of ARID1A in tumor cells enhanced the response of inflammatory chemokines. In conclusion, this study demonstrates that ARID1A is a direct target of miR-185 in COAD that regulates the immune modulations in the microenvironment of COAD.
- Subjects :
- 0301 basic medicine
Cancer Research
Tumor suppressor gene
ARID1A
Colorectal cancer
AT-rich interaction domain 1A (ARID1A)
posttranscriptional regulation
miR-185-5P
03 medical and health sciences
0302 clinical medicine
Breast cancer
medicine
Survival rate
RC254-282
Original Research
Tumor microenvironment
business.industry
The Cancer Genome Atlas (TCGA)
immune cell infiltration
Cancer
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
medicine.disease
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
Cancer research
gene expression
Ovarian cancer
business
Subjects
Details
- Language :
- English
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Frontiers in Oncology
- Accession number :
- edsair.doi.dedup.....8e38ee0637affe99434e7660a782493a
- Full Text :
- https://doi.org/10.3389/fonc.2021.679334/full