NOVA1 inhibition by miR-146b-5p in the remnant tissue microenvironment defines occult residual disease after gastric cancer removalopen access
- Authors
- Yoon, Sun Och; Kim, Eun Kyung; Lee, Mira; Jung, Woon Yong; Lee, Hyunjoo; Kang, Youngran; Jang, You-Jin; Hong, Soon Won; Choi, Seung Ho; Yang, Woo Ick
- Issue Date
- Jan-2016
- Publisher
- IMPACT JOURNALS LLC
- Keywords
- microenvironment; residual disease; hsa-microRNA-146b-5p; NOVA1; stromal cells
- Citation
- ONCOTARGET, v.7, no.3, pp.2475 - 2495
- Indexed
- SCIE
SCOPUS
- Journal Title
- ONCOTARGET
- Volume
- 7
- Number
- 3
- Start Page
- 2475
- End Page
- 2495
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/155262
- DOI
- 10.18632/oncotarget.6542
- ISSN
- 1949-2553
- Abstract
- Occult residual disease in remnant tissues could be the cause of tumor relapse. To identify signal molecules and target cells that may be indicative of occult residual disease within a remnant microenvironment, proximal resection margin tissues of gastric cancers were used, as these correspond to the nearest remnant tissues after gastrectomy. Increased miR-146b-5p in the remnant microenvironment was determined to be a strong risk factor for tumor relapse and poor survival rate. NOVA1, a target gene of miR-146b-5p, was decreased in remnant tissues of patients with a poor prognosis. NOVA1 was enriched in stromal spindle cells such as fibroblasts within normal tissues. In non-neoplastic inflammation, such as gastritis, NOVA1 was highly enriched in T lymphocytes and stromal spindle cells, while expression of this protein was frequently decreased in those types of cells within gastric cancer tissues. Particularly, decreased NOVA1 in T cells within the gastric cancer tissues was correlated with decreased FOXP3-positive regulatory T cells and was associated with poor patient prognosis. In vitro analysis showed that the NOVA1 gene was inhibited by miR-146b-5p. In immune cells as well as stromal spindle cells, decreased NOVA1, possibly inhibited by miR-146b-5p, is a candidate biomarker predicting poor prognosis of gastric cancer patients and is also a biomarker of occult residual disease in remnant tissues after gastric cancer removal.
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