miR-146b-5p mediates p16-dependent repression of IL-6 and suppresses paracrine procarcinogenic effects of breast stromal fibroblasts

Oncotarget
Mysoon M Al-Ansari, Abdelilah Aboussekhra

Abstract

Increasing evidence support the critical roles of active stromal fibroblasts in breast cancer development and spread. However, the mediators and the mechanisms of regulation are still not well defined. We have shown here that the tumor suppressor p16(INK4A) protein inhibits the pro-carcinogenic effects of breast stromal fibroblasts through repressing the expression/secretion of IL-6. Indeed, p16(INK4A) suppresses IL-6 at the mRNA and protein levels. This effect is mediated trough miR-146b-5p, which inhibits IL-6 expression through a specific sequence at the IL-6 3'UTR. In addition, we present clear evidence that miR-146b-5p inhibition is sufficient to transactivate breast stromal fibroblasts, which promote epithelial-to-mesenchymal-transition in breast cancer cells in a paracrine manner. By contrast, ectopic expression of miR-146b-5p in active fibroblasts abrogated their pro-carcinogenic effects. The physiological importance of miR-146b-5p inhibition was revealed by showing that the levels of pre-miR-146b-5p as well as its mature form are reduced in cancer-associated fibroblasts as compared with their normal adjacent counterparts from cancer-free tissues isolated from the same patients. Interestingly, treatment of active breast...Continue Reading

References

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Citations

Oct 20, 2017·Oncology Reports·Zhenwei QiuChongbing Sun
Nov 10, 2018·Oncotarget·Mysoon M Al-Ansari, Abdelilah Aboussekhra
May 18, 2020·Breast Cancer Research : BCR·Mysoon M Al-AnsariAbdelilah Aboussekhra
Aug 2, 2017·International Journal of Immunopathology and Pharmacology·Chun-Mei WangBo Bai
Aug 31, 2017·Molecular Cancer·Fengming YangHua Shen
Sep 13, 2018·Journal of Cellular Biochemistry·Gaopei MengNa Xiao
Jul 19, 2018·Oncotarget·Shariq S KhwajaJiayi Huang
Oct 9, 2019·Applied Immunohistochemistry & Molecular Morphology : AIMM·Aparna HarbhajankaPaolo Gattuso
Apr 27, 2019·Journal of Cellular Physiology·Alireza BahiraeeJafar Amani
Apr 7, 2020·Expert Opinion on Therapeutic Targets·Rosamaria LappanoErnestina Marianna De Francesco
Dec 15, 2017·Journal of Cellular Physiology·Mahdi RivandiAmir Avan
Dec 15, 2020·Human Gene Therapy·Motahareh Sheikh-HosseiniBabak Arjmand
May 18, 2020·International Immunopharmacology·Gholamreza Rezaei DanbaranHamed Mohammadi
Dec 12, 2020·Acta Pharmaceutica Sinica. B·Rujing ChenKaili Hu

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Methods Mentioned

BETA
flow cytometry
ELISA

Software Mentioned

Cell Quest

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