The miR-16 microRNA precursor family is a group of related small
non-coding RNA genes that regulates
gene expression. miR-16, miR-15, mir-195 and miR-497 are related
microRNA precursor sequences from the mir-15
gene family (
[1]). This microRNA family appears to be
vertebrate specific and its members have been predicted or experimentally validated in a wide range of vertebrate species (
MIPF0000006).
In the original publication which identified the action of miR15 and miR16 in the development of
B-CLL, Calin and colleagues proposed that miR16 could be the targets with imperfect base pairing for 14 genes.[1] Increased
CD5+B-lymphocytes in
CLL suggests the miR16 may be involved in
cellular differentiation.[1] In
animal models single-stranded microRNA species act by
binding to imperfect
mRNAcomplements, typically to the
3' UTR,[15][16] although targets have also been observed in the
coding sequence of the
mRNA.[15][17]Downregulation of miR16 (as well as miR15) was observed in
diffuse large B-cell lymphoma.[18]miR16 has been shown to bind to a nine
base pair to a complementary sequence in the
3' UTR region of
BCL2, which is an anti-
apoptotic gene involved in an
evolutionarily conserved pathway in
programmed cell death.[19] In the nasopharyngeal carcinoma cell line, miR-16 has been shown to target the 3' UTR of vascular endothelial growth factor (VEGF) and repress the expression of VEGF, which is an important angiogenic factor.[20][21]
miR-16 and miR-15a are clustered within a 0.5
kbp region in
Chromosome 13 (13q14) in humans, a chromosomal region shown to be deleted or down-regulated in approximately more than half of
B-CLL,[1] the most prevalent form of leukemia in adults.[41]Carcinogenesis is a gradual process, involving multiple genetic
mutations, thus every patient with
malignancy presents with a
heterogeneous population of
cells. The fact that mir-16 microRNA loss is observed in a large proportion of cells indicates the change occurred early in
cancer development[23] and a target for
therapeutic intervention.
^Dong JT, Boyd JC, Frierson HF Jr (2001). "Loss of heterozygosity at 13q14 and 13q21 in high grade, high stage prostate cancer". Prostate. 49 (3): 166–171.
doi:
10.1002/pros.1131.
PMID11746261.
S2CID40075043.
^Liu Y, Corcoran M, Rasool O, Ivanova G, Ibbotson R, Grander D, Iyengar A, Baranova A, Kashuba V, Merup M, Wu XS, Gardiner A, Mullenbach R, Poltaraus A, Hultstrom AL, Juliusson G, Chapman R, Tiller M, Cotter F, Gahrton G, Yankovsky N, Zabarovsky E, Einhorn S, Oscier D (1997). "Cloning of two candidate tumor suppressor genes within a 10 kb region on chromosome 13q14, frequently deleted in chronic lymphocytic leukemia". Oncogene. 15 (20): 2463–2473.
doi:
10.1038/sj.onc.1201643.
PMID9395242.
S2CID21133945.
^Rondeau G, Moreau I, Bézieau S, Petit JL, Heilig R, Fernandez S, Pennarun E, Myers JS, Batzer MA, Moisan JP, Devilder MC (2001). "Comprehensive analysis of a large genomic sequence at the putative B-cell chronic lymphocytic leukaemia (B-CLL) tumour suppresser gene locus". Mutat Res. 458 (3–4): 55–70.
doi:
10.1016/S0027-5107(01)00219-6.
PMID11691637.
^Ciafrè SA, Galardi S, Mangiola A, Ferracin M, Liu CG, Sabatino G, Negrini M, Maira G, Croce CM, Farace MG (2005). "Extensive modulation of a set of microRNAs in primary glioblastoma". Biochem Biophys Res Commun. 334 (4): 1351–1358.
doi:
10.1016/j.bbrc.2005.07.030.
PMID16039986.
^Metzler M, Wilda M, Busch K, Viehmann S, Borkhardt A (2004). "High expression of precursor microRNA-155/BIC RNA in children with Burkitt's lymphoma". Genes Chromosomes Cancer. 39 (2): 167–169.
doi:
10.1002/gcc.10316.
PMID14695998.
S2CID10009892.
^Bonci D, Coppola V, Musumeci M, Addario A, Giuffrida R, Memeo L, D'Urso L, Pagliuca A, Biffoni M, Labbaye C, Bartucci M, Muto G, Peschle C, De Maria R (2008). "The miR-15a-miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities". Nat Med. 14 (11): 1271–1277.
doi:
10.1038/nm.1880.
PMID18931683.
S2CID1452987.
^Liu W, Liu C, Zhu J, Shu P, Yin B, Gong Y, Qiang B, Yuan J, Peng X (2010). "MicroRNA-16 targets amyloid precursor protein to potentially modulate Alzheimer's-associated pathogenesis in SAMP8 mice". Neurobiol Aging. 33 (3): 522–534.
doi:
10.1016/j.neurobiolaging.2010.04.034.
PMID20619502.
S2CID12138856.
^Yang J, Cao Y, Sun J, Zhang Y (2009). "Curcumin reduces the expression of Bcl-2 by upregulating miR-15a and miR-16 in MCF-7 cells". Med Oncol. 27 (4): 1114–8.
doi:
10.1007/s12032-009-9344-3.
PMID19908170.
S2CID21826528.
^Guo CJ, Pan Q, Jiang B, Chen GY, Li DG (2009). "Effects of upregulated expression of microRNA-16 on biological properties of culture-activated hepatic stellate cells". Apoptosis. 14 (11): 1331–40.
doi:
10.1007/s10495-009-0401-3.
PMID19784778.
S2CID3229011.
^Lerner M, Harada M, Lovén J, Castro J, Davis Z, Oscier D, Henriksson M, Sangfelt O, Grandér D, Corcoran MM (2009). "DLEU2, frequently deleted in malignancy, functions as a critical host gene of the cell cycle inhibitory microRNAs miR-15a and miR-16-1". Exp Cell Res. 315 (17): 2941–52.
doi:
10.1016/j.yexcr.2009.07.001.
PMID19591824.
^Tsang WP, Kwok TT (2010). "Epigallocatechin gallate up-regulation of miR-16 and induction of apoptosis in human cancer cells". J Nutr Biochem. 21 (2): 140–6.
doi:
10.1016/j.jnutbio.2008.12.003.
PMID19269153.
^Guo CJ, Pan Q, Li DG, Sun H, Liu BW (2009). "miR-15b and miR-16 are implicated in activation of the rat hepatic stellate cell: An essential role for apoptosis". J Hepatol. 50 (4): 766–78.
doi:
10.1016/j.jhep.2008.11.025.
PMID19232449.
^Kaddar T, Chien WW, Bertrand Y, Pages MP, Rouault JP, Salles G, Ffrench M, Magaud JP (2009). "Prognostic value of miR-16 expression in childhood acute lymphoblastic leukemia relationships to normal and malignant lymphocyte proliferation". Leuk Res. 33 (9): 1217–23.
doi:
10.1016/j.leukres.2008.12.015.
PMID19195700.
The miR-16 microRNA precursor family is a group of related small
non-coding RNA genes that regulates
gene expression. miR-16, miR-15, mir-195 and miR-497 are related
microRNA precursor sequences from the mir-15
gene family (
[1]). This microRNA family appears to be
vertebrate specific and its members have been predicted or experimentally validated in a wide range of vertebrate species (
MIPF0000006).
In the original publication which identified the action of miR15 and miR16 in the development of
B-CLL, Calin and colleagues proposed that miR16 could be the targets with imperfect base pairing for 14 genes.[1] Increased
CD5+B-lymphocytes in
CLL suggests the miR16 may be involved in
cellular differentiation.[1] In
animal models single-stranded microRNA species act by
binding to imperfect
mRNAcomplements, typically to the
3' UTR,[15][16] although targets have also been observed in the
coding sequence of the
mRNA.[15][17]Downregulation of miR16 (as well as miR15) was observed in
diffuse large B-cell lymphoma.[18]miR16 has been shown to bind to a nine
base pair to a complementary sequence in the
3' UTR region of
BCL2, which is an anti-
apoptotic gene involved in an
evolutionarily conserved pathway in
programmed cell death.[19] In the nasopharyngeal carcinoma cell line, miR-16 has been shown to target the 3' UTR of vascular endothelial growth factor (VEGF) and repress the expression of VEGF, which is an important angiogenic factor.[20][21]
miR-16 and miR-15a are clustered within a 0.5
kbp region in
Chromosome 13 (13q14) in humans, a chromosomal region shown to be deleted or down-regulated in approximately more than half of
B-CLL,[1] the most prevalent form of leukemia in adults.[41]Carcinogenesis is a gradual process, involving multiple genetic
mutations, thus every patient with
malignancy presents with a
heterogeneous population of
cells. The fact that mir-16 microRNA loss is observed in a large proportion of cells indicates the change occurred early in
cancer development[23] and a target for
therapeutic intervention.
^Dong JT, Boyd JC, Frierson HF Jr (2001). "Loss of heterozygosity at 13q14 and 13q21 in high grade, high stage prostate cancer". Prostate. 49 (3): 166–171.
doi:
10.1002/pros.1131.
PMID11746261.
S2CID40075043.
^Liu Y, Corcoran M, Rasool O, Ivanova G, Ibbotson R, Grander D, Iyengar A, Baranova A, Kashuba V, Merup M, Wu XS, Gardiner A, Mullenbach R, Poltaraus A, Hultstrom AL, Juliusson G, Chapman R, Tiller M, Cotter F, Gahrton G, Yankovsky N, Zabarovsky E, Einhorn S, Oscier D (1997). "Cloning of two candidate tumor suppressor genes within a 10 kb region on chromosome 13q14, frequently deleted in chronic lymphocytic leukemia". Oncogene. 15 (20): 2463–2473.
doi:
10.1038/sj.onc.1201643.
PMID9395242.
S2CID21133945.
^Rondeau G, Moreau I, Bézieau S, Petit JL, Heilig R, Fernandez S, Pennarun E, Myers JS, Batzer MA, Moisan JP, Devilder MC (2001). "Comprehensive analysis of a large genomic sequence at the putative B-cell chronic lymphocytic leukaemia (B-CLL) tumour suppresser gene locus". Mutat Res. 458 (3–4): 55–70.
doi:
10.1016/S0027-5107(01)00219-6.
PMID11691637.
^Ciafrè SA, Galardi S, Mangiola A, Ferracin M, Liu CG, Sabatino G, Negrini M, Maira G, Croce CM, Farace MG (2005). "Extensive modulation of a set of microRNAs in primary glioblastoma". Biochem Biophys Res Commun. 334 (4): 1351–1358.
doi:
10.1016/j.bbrc.2005.07.030.
PMID16039986.
^Metzler M, Wilda M, Busch K, Viehmann S, Borkhardt A (2004). "High expression of precursor microRNA-155/BIC RNA in children with Burkitt's lymphoma". Genes Chromosomes Cancer. 39 (2): 167–169.
doi:
10.1002/gcc.10316.
PMID14695998.
S2CID10009892.
^Bonci D, Coppola V, Musumeci M, Addario A, Giuffrida R, Memeo L, D'Urso L, Pagliuca A, Biffoni M, Labbaye C, Bartucci M, Muto G, Peschle C, De Maria R (2008). "The miR-15a-miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities". Nat Med. 14 (11): 1271–1277.
doi:
10.1038/nm.1880.
PMID18931683.
S2CID1452987.
^Liu W, Liu C, Zhu J, Shu P, Yin B, Gong Y, Qiang B, Yuan J, Peng X (2010). "MicroRNA-16 targets amyloid precursor protein to potentially modulate Alzheimer's-associated pathogenesis in SAMP8 mice". Neurobiol Aging. 33 (3): 522–534.
doi:
10.1016/j.neurobiolaging.2010.04.034.
PMID20619502.
S2CID12138856.
^Yang J, Cao Y, Sun J, Zhang Y (2009). "Curcumin reduces the expression of Bcl-2 by upregulating miR-15a and miR-16 in MCF-7 cells". Med Oncol. 27 (4): 1114–8.
doi:
10.1007/s12032-009-9344-3.
PMID19908170.
S2CID21826528.
^Guo CJ, Pan Q, Jiang B, Chen GY, Li DG (2009). "Effects of upregulated expression of microRNA-16 on biological properties of culture-activated hepatic stellate cells". Apoptosis. 14 (11): 1331–40.
doi:
10.1007/s10495-009-0401-3.
PMID19784778.
S2CID3229011.
^Lerner M, Harada M, Lovén J, Castro J, Davis Z, Oscier D, Henriksson M, Sangfelt O, Grandér D, Corcoran MM (2009). "DLEU2, frequently deleted in malignancy, functions as a critical host gene of the cell cycle inhibitory microRNAs miR-15a and miR-16-1". Exp Cell Res. 315 (17): 2941–52.
doi:
10.1016/j.yexcr.2009.07.001.
PMID19591824.
^Tsang WP, Kwok TT (2010). "Epigallocatechin gallate up-regulation of miR-16 and induction of apoptosis in human cancer cells". J Nutr Biochem. 21 (2): 140–6.
doi:
10.1016/j.jnutbio.2008.12.003.
PMID19269153.
^Guo CJ, Pan Q, Li DG, Sun H, Liu BW (2009). "miR-15b and miR-16 are implicated in activation of the rat hepatic stellate cell: An essential role for apoptosis". J Hepatol. 50 (4): 766–78.
doi:
10.1016/j.jhep.2008.11.025.
PMID19232449.
^Kaddar T, Chien WW, Bertrand Y, Pages MP, Rouault JP, Salles G, Ffrench M, Magaud JP (2009). "Prognostic value of miR-16 expression in childhood acute lymphoblastic leukemia relationships to normal and malignant lymphocyte proliferation". Leuk Res. 33 (9): 1217–23.
doi:
10.1016/j.leukres.2008.12.015.
PMID19195700.