Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Dec 15;13(12):6147-6175.
eCollection 2023.

MicroRNA-183 cluster: a promising biomarker and therapeutic target in gastrointestinal malignancies

Yufei Zheng  1 , Olga Sukocheva  2 , Edmund Tse  2 , Margarita Neganova  3   4 , Yulia Aleksandrova  3   4 , Ruiwen Zhao  1 , Vladimir Chubarev  5 , Ruitai Fan  1 , Junqi Liu  1
Affiliations
Review

MicroRNA-183 cluster: a promising biomarker and therapeutic target in gastrointestinal malignancies

Yufei Zheng et al. Am J Cancer Res. .

Abstract

Small non-coding RNAs (microRNA, miR), powerful epigenetic regulators, were found involved in the regulation of most biological functions via post-translational inhibition of protein expression. Increased expression of pro-oncogenic miRs (known as miR cancer biomarkers) and inhibition of pro-apoptotic miR expression have been demonstrated in different tumors. The recently identified miR-183 was found implicated in gastrointestinal tumor metabolism regulation. Elevated miR-183 expression and cancer-promoting effects were reported in esophageal and colorectal cancers, which was partially contradicted by controversial data observed in gastric cancers. Anti-cancer effect of miR-183 in gastric cancer cells was associated with the Bim-1 and Ezrin genes regulation. Many studies indicated that miR-183 can inhibit tumor suppressor genes in most cell lines, promoting tumor cell proliferation and migration. Increased miR-183 level results in the downregulation of FOXO1, PDCD4, and other tumor suppressor genes in gastrointestinal tumor cells. MiR-183 also influences the signaling of PI3K/AKT/mTOR, Wnt/β-catenin, and Bcl-2/p53 signaling pathways. Mir-183 inhibits apoptosis and autophagy, and promotes epithelial-to-mesenchymal transition, cancer cell proliferation, and migration. Accordingly, gastrointestinal cancer occurrence, development of chemoradiotherapy resistance, recurrence/metastasis, and prognosis were associated with miR-183 expression. The current study assessed reported miR-183 functions and signaling, providing new insights for the diagnosis and treatment of gastrointestinal malignancies.

Keywords: MicroRNA (miR); cancer biomarker; epigenetics; esophageal cancer; gastrointestinal malignancy; miR-182; miR-183; miR-96.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
MiR-183/96/182 cluster signaling is activated by Wnt/β-catenin pathway and associated with oncogenic transformation, cell cycle disorders, evasion of cell death, and development of drug resistance in GI cancers. Inhibition of the miR-183 signaling was shown to suppress tumorigenesis. Inhibition of miR-183C signaling was linked to the regulation of FoxF2, RCN2, and DAB2IP (the cluster targets) upstream of Wnt, leading to the and inhibition of cancer progression.
Figure 2
Figure 2
Dual role of miR-183 signaling in GCs. Various targets, including NF-κB, PDCD4, FOXO1, VEGFR, PI3K/AKT/mTOR, MMP-2/9, TGF-β, FHL1, MUC15, ATG5, and TPM1 were associated with the tumor promoting effects of miR-183. Anti-oncogenic and tumor suppressive roles of miR-183 were correlated with the inhibition of Ezrin (actin-binding scaffold protein), Bmi-1, EEF2, ANUBL1, NF-κB, JNK, and activation of immune responses (NKG2D signaling).
Figure 3
Figure 3
Molecular regulation of miR-183/96/182 cluster in GI malignancies.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–249. - PubMed
    1. Wong MCS, Huang J, Lok V, Wang J, Fung F, Ding H, Zheng ZJ. Differences in incidence and mortality trends of colorectal cancer worldwide based on sex, age, and anatomic location. Clin Gastroenterol Hepatol. 2021;19:955–966. e61. - PubMed
    1. Coccolini F, Nardi M, Montori G, Ceresoli M, Celotti A, Cascinu S, Fugazzola P, Tomasoni M, Glehen O, Catena F, Yonemura Y, Ansaloni L. Neoadjuvant chemotherapy in advanced gastric and esophago-gastric cancer. Meta-analysis of randomized trials. Int J Surg. 2018;51:120–127. - PubMed
    1. Kelly RJ. Emerging multimodality approaches to treat localized esophageal cancer. J Natl Compr Canc Netw. 2019;17:1009–1014. - PubMed
    1. Abnet CC, Arnold M, Wei WQ. Epidemiology of esophageal squamous cell carcinoma. Gastroenterology. 2018;154:360–373. - PMC - PubMed

LinkOut - more resources