title: miR-125b promotes cell death by targeting spindle assembly checkpoint gene MAD1 and modulating mitotic progression.
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.
authors.affiliation: Cancer Biology and Inflammatory Disorder Division, Indian Institute of Chemical Biology, Council of Scientific and Industrial Research, 4 Raja SC Mullick Road, Kolkata, India.
authors.forename: S
authors.initials: S
authors.lastname: Bhattacharjya
authors.forename: S
authors.initials: S
authors.lastname: Nath
authors.forename: J
authors.initials: J
authors.lastname: Ghose
authors.forename: G P
authors.initials: GP
authors.lastname: Maiti
authors.forename: N
authors.initials: N
authors.lastname: Biswas
authors.forename: S
authors.initials: S
authors.lastname: Bandyopadhyay
authors.forename: C K
authors.initials: CK
authors.lastname: Panda
authors.forename: N P
authors.initials: NP
authors.lastname: Bhattacharyya
authors.forename: S
authors.initials: S
authors.lastname: Roychoudhury
mesh_terms: D020413:3' Untranslated Regions; D000705:Anaphase; D017209:Apoptosis; D001483:Base Sequence; D002135:Calcium-Binding Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002869:Chromosome Aberrations; D015536:Down-Regulation; D045325:HCT116 Cells; D056945:Hep G2 Cells; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints; D064246:Mad2 Proteins; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; C501384:MAD1L1 protein, human; C577697:MAD2L1 protein, human; C531888:MIRN125 microRNA, human; D064246:Mad2 Proteins; D035683:MicroRNAs; D009687:Nuclear Proteins; D012097:Repressor Proteins