miR-200c Modulates the Pathogenesis of Radiation-Induced Oral Mucositis

Joint Authors

Sharma, Sherven
Tao, Jingjing
Fan, Mengjing
Zhou, Difan
Hong, Yiyang
Zhang, Jing
Liu, Hai
Wang, Guanyu
Dong, Qinghua

Source

Oxidative Medicine and Cellular Longevity

Issue

Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-14, 14 p.

Publisher

Hindawi Publishing Corporation

Publication Date

2019-06-27

Country of Publication

Egypt

No. of Pages

14

Main Subjects

Biology

Abstract EN

Radiation-induced oral mucositis (RIOM) is one of the most common side effects of radiotherapy in cancer patients, especially in almost all head and neck cancer patients.

It presents as severe pain and ulceration.

The development of RIOM is composed of five stages: initiation, primary damage response, signal amplification, ulceration, and healing.

However, the key regulators involved in the RIOM pathogenesis remain largely unknown.

In this study, we reveal a novel role of miR-200c, a member of the miR-200 family, in modulating RIOM pathogenesis.

Using a mouse model mimicking RIOM, we found that the miR-200 family numbers (miR-141, miR-200a, miR-200b, and miR-200c) except miR-429 were significantly induced during the RIOM formation.

Besides, in RIOM mice, miR-200c expression level was also increased dramatically in the normal human keratinocytes (NHKs) after irradiation.

Knockdown of miR-200c expression with miR-200c-3p-shRNA significantly reduced senescence phenotype and enhanced cell proliferation in NHKs after irradiation.

The generation of reactive oxygen species (ROS) and p47 enzyme involved in ROS production was increased after irradiation but both were markedly reduced in NHKs by miR-200c inhibition.

Knockdown of miR-200c expression in NHKs increased DNA double-strand break repair after irradiation compared with control NHKs.

Furthermore, miR-200c inhibition repressed the production of proinflammatory cytokines (TGF-β, TNF-α, and IL-1α) via inhibiting NF-κB and Smad2 activation in NHKs exposed to IR.

Additionally, miR-200c inhibition promoted NHK migration and increased the expression of molecules that regulate epithelial to mesenchymal transition, including Snail, Vimentin, Zeb1, and Bmi-1.

These results not only identify the key role of miR-200c in the pathogenesis of RIOM but also provide a novel therapeutic target to treat RIOM.

American Psychological Association (APA)

Tao, Jingjing& Fan, Mengjing& Zhou, Difan& Hong, Yiyang& Zhang, Jing& Liu, Hai…[et al.]. 2019. miR-200c Modulates the Pathogenesis of Radiation-Induced Oral Mucositis. Oxidative Medicine and Cellular Longevity،Vol. 2019, no. 2019, pp.1-14.
https://search.emarefa.net/detail/BIM-1202627

Modern Language Association (MLA)

Tao, Jingjing…[et al.]. miR-200c Modulates the Pathogenesis of Radiation-Induced Oral Mucositis. Oxidative Medicine and Cellular Longevity No. 2019 (2019), pp.1-14.
https://search.emarefa.net/detail/BIM-1202627

American Medical Association (AMA)

Tao, Jingjing& Fan, Mengjing& Zhou, Difan& Hong, Yiyang& Zhang, Jing& Liu, Hai…[et al.]. miR-200c Modulates the Pathogenesis of Radiation-Induced Oral Mucositis. Oxidative Medicine and Cellular Longevity. 2019. Vol. 2019, no. 2019, pp.1-14.
https://search.emarefa.net/detail/BIM-1202627

Data Type

Journal Articles

Language

English

Notes

Includes bibliographical references

Record ID

BIM-1202627