miR-125b promotes cell death by targeting spindle assembly checkpoint gene MAD1 and modulating mitotic progression

Bhattacharjya, S. ; Nath, S. ; Ghose, J. ; Maiti, G. P. ; Biswas, N. ; Bandyopadhyay, S. ; Panda, C. K. ; Bhattacharyya, N. P. ; Roychoudhury, S. (2013) miR-125b promotes cell death by targeting spindle assembly checkpoint gene MAD1 and modulating mitotic progression Cell Death and Differentiation, 20 (3). pp. 430-442. ISSN 1350-9047

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Official URL: http://www.nature.com/cdd/journal/v20/n3/abs/cdd20...

Related URL: http://dx.doi.org/10.1038/cdd.2012.135

Abstract

The spindle assembly checkpoint (SAC) is a ‘wait-anaphase’ mechanism that has evolved in eukaryotic cells in response to the stochastic nature of chromosome–spindle attachments. In the recent past, different aspects of the SAC regulation have been described. However, the role of microRNAs in the SAC is vaguely understood. We report here that Mad1, a core SAC protein, is repressed by human miR-125b. Mad1 serves as an adaptor protein for Mad2 – which functions to inhibit anaphase entry till the chromosomal defects in metaphase are corrected. We show that exogenous expression of miR-125b, through downregulation of Mad1, delays cells at metaphase. As a result of this delay, cells proceed towards apoptotic death, which follows from elevated chromosomal abnormalities upon ectopic expression of miR-125b. Moreover, expressions of Mad1 and miR-125b are inversely correlated in a variety of cancer cell lines, as well as in primary head and neck tumour tissues. We conclude that increased expression of miR-125b inhibits cell proliferation by suppressing Mad1 and activating the SAC transiently. We hypothesize an optimum Mad1 level and thus, a properly scheduled SAC is maintained partly by miR-125b.

Item Type:Article
Source:Copyright of this article belongs to Nature Publishing Group.
Keywords:miR-125b; Spindle Assembly Checkpoint; MAD1; Apoptosis; Mitotic Delay; Chromosomal Abnormalities
ID Code:105982
Deposited On:21 Dec 2017 11:37
Last Modified:21 Dec 2017 11:37

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