DICER1
MIM.606241 14q31
DICER1 is a gene encoding an endoribonuclease critical to the generation of small noncoding regulatory RNAs.
Human DICER1 protein possesses an RNA helicase motif containing a DEXH box in its amino terminus and an RNA motif in the carboxy terminus.
DICER1, also known as helicase-MOI, is required by the RNA interference and small temporal RNA (stRNA) pathways to produce the active small RNA component that represses gene expression.
In RNA interference, the RNase-III enzyme Dicer processes exogenous double-stranded RNA into small interfering RNAs (siRNAs). siRNAs guide RNA-induced silencing complexes to cleave homologous transcripts, enabling gene-specific knock-down.
In plants, double-stranded RNA is processed into siRNA species of 21 nucleotides (nt) and 24 nt, but, unlike in nematodes, the Dicer enzymes involved in this processing have not been identified.
Additionally, in both plants and nematodes, systemic signals with RNA components convey the sequence-specific effects of RNA interference between cells.
Function
Dicer is required for Sertoli cell function and survival. Kim GJ, Georg I, Scherthan H, Merkenschlager M, Guillou F, Scherer G, Barrionuevo F. Int J Dev Biol. 2010;54(5):867-75. PMID: #19876815#
Pathology
germline mutations of DICER1 in pleuropulmonary blastoma (PPB) +/- some of whom include cases of multinodular goiter and gonadal tumors such as ovarian Sertoli-Leydig cell tumors.
- PPBs consist of mesenchymal cells that are susceptible to malignant transformation and cysts lined by epithelial cells. In a subset of patients, overgrowth of the cysts by mesenchymal cells leads to sarcoma formation.
Germline DICER1 mutations in familial cystic nephroma. (#21036787#)
Constitutional DICER1 haploinsufficiency predisposes to a broad range of tumours (DICER1 syndrome), making a substantial contribution to PPB, cystic nephroma and ovarian Sertoli-Leydig tumours, but a smaller contribution to other tumours. (#21266384#)
Expression of DICER1 protein was undetectable in the epithelial component of PPB tumors but was retained in the malignant mesenchyme (sarcoma).
DICER1 mutations are associated with both familial multinodular goiter and multinodular goite with ovarian Sertoli-Leydig cell tumors, independent of pleuropulmonary blastoma (PPB). (#21205968#)
Lower DICER1 transcript levels are correlated with disease recurrence and worse DFS survival in patients with endometrioid endometrial cancer. The factors that influence DICER1 transcript levels in primary endometrial cancers remain unknown. (#21061369#)
MicroRNA-107, an Oncogene MicroRNA that Regulates Tumor Invasion and Metastasis By Targeting DICER1 in Gastric Cancer: MiR-107 promotes gastric cancer invasion and metastasis. (#21029372#)
Dicer1 functions as a haploinsufficient tumor suppressor. (#19903759#)
References
DICER1 syndrome: clarifying the diagnosis, clinical features and management implications of a pleiotropic tumour predisposition syndrome. Slade I, Bacchelli C, Davies H, Murray A, Abbaszadeh F, Hanks S, Barfoot R, Burke A, Chisholm J, Hewitt M, Jenkinson H, King D, Morland B, Pizer B, Prescott K, Saggar A, Side L, Traunecker H, Vaidya S, Ward P, Futreal PA, Vujanic G, Nicholson AG, Sebire N, Turnbull C, Priest JR, Pritchard-Jones K, Houlston R, Stiller C, Stratton MR, Douglas J, Rahman N. J Med Genet. 2011 Jan 25. PMID: #21266384#
DICER1 mutations in familial multinodular goiter with and without ovarian Sertoli-Leydig cell tumors. Rio Frio T, Bahubeshi A, Kanellopoulou C, Hamel N, Niedziela M, Sabbaghian N, Pouchet C, Gilbert L, O’Brien PK, Serfas K, Broderick P, Houlston RS, Lesueur F, Bonora E, Muljo S, Schimke RN, Bouron-Dal Soglio D, Arseneau J, Schultz KA, Priest JR, Nguyen VH, Harach HR, Livingston DM, Foulkes WD, Tischkowitz M. JAMA. 2011 Jan 5;305(1):68-77. PMID: #21205968#
Germline DICER1 mutations and familial cystic nephroma. Bahubeshi A, Bal N, Frio TR, Hamel N, Pouchet C, Yilmaz A, Bouron-Dal Soglio D, Williams GM, Tischkowitz M, Priest JR, Foulkes WD. J Med Genet. 2010 Dec;47(12):863-6. PMID: #21036787#
DICER1 expression and outcomes in endometrioid endometrial adenocarcinoma. Zighelboim I, Reinhart AJ, Gao F, Schmidt AP, Mutch DG, Thaker PH, Goodfellow PJ. Cancer. 2010 Nov 8. PMID: #21061369#
MicroRNA-107, an Oncogene MicroRNA that Regulates Tumor Invasion and Metastasis By Targeting DICER1 in Gastric Cancer: MiR-107 promotes gastric cancer invasion and metastasis. Li X, Zhang Y, Shi Y, Dong G, Liang J, Han Y, Wang X, Zhao Q, Ding J, Wu K, Fan D. J Cell Mol Med. 2010 Oct 3. PMID: #21029372#
Dicer1 functions as a haploinsufficient tumor suppressor. Kumar MS, Pester RE, Chen CY, Lane K, Chin C, Lu J, Kirsch DG, Golub TR, Jacks T. Genes Dev. 2009 Dec 1;23(23):2700-4. PMID: #19903759# (Free)
DICER1 Mutations in Familial Pleuropulmonary Blastoma. Hill DA, Ivanovich J, Priest JR, Gurnett CA, Dehner LP, Desruisseau D, Jarzembowski JA, Wikenheiser-Brokamp KA, Suarez BK, Whelan AJ, Williams G, Bracamontes D, Messinger Y, Goodfellow PJ. Science. 2009 Jun 25. PMID: #19556464# (Free)