000			02156nam a2200313Ia 4500
003			MX-MdCICY
005			20251009160707.0
040			_cCICY
090			_aB-21857
245	1	0	_aElevated snoRNA biogenesis is essential in breast cancer
490	0		_aOncogene, 33(1), p.1348-1358, 2014
500			_aArtículo
520	3		_aHyperactive ribosomal biogenesis is widely observed in cancer, which has been partly attributed to the increased rDNA transcription by Pol I in cancer. However, whether small nucleolar RNAs (snoRNAs), a class of non-coding RNAs crucial in ribosomal RNA (rRNA) maturation and functionality, are involved in cancer remains elusive. We report that snoRNAs and fibrillarin (FBL, an enzymatic small nucleolar ribonucleoprotein, snoRNP) are frequently overexpressed in both murine and human breast cancer as well as in prostate cancers, and significantly, that this overexpression is essential for tumorigenicity in vitro and in vivo. We demonstrate that when the elevated snoRNA pathway is suppressed, the tumor suppressor p53 can act as a sentinel of snoRNP perturbation, the activation of which mediates the growth inhibitory effect. On the other hand, high level of FBL interferes with the activation of p53 by stress. We further show that p53 activation by FBL knockdown is not only regulated by the ribosomal protein[1]MDM2-mediated protein stabilization pathway, but also by enhanced PTB-dependent, cap-independent translation. Together, our data uncover an essential role of deregulated snoRNA biogenesis in tumors and a new mechanism of nucleolar modulation of p53.
650	1	4	_aBREAST CÁNCER
650	1	4	_aFIBRILLARIN
650	1	4	_aNUCLEOLAR STRESS
650	1	4	_aP53
650	1	4	_aSNORNA
700	1	2	_aSu, H.
700	1	2	_aXu, T.
700	1	2	_aGanapathy, S.
700	1	2	_aShadfan, M.
700	1	2	_aLong, M.
700	1	2	_aHuang, T. H.
700	1	2	_aYuan, Z. M.
856	4	0	_uhttps://drive.google.com/file/d/13fa2NBfRE9kE1HhmVshhkMbRMznjpyf2/view?usp=drive_link _zPara ver el documento ingresa a Google con tu cuenta: @cicy.edu.mx
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