micrornas in molecular medicine - lc sciences llc · wl, massagué j. endogenous human micrornas...
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microRNAs in Molecular MedicinemicroRNAs in Molecular MedicinemicroRNAs in Molecular MedicineSelected Publications by LC Sciences’ CustomersSelected Publications by LC Sciences CustomersSelected Publications by LC Sciences Customers
LC Sciences LLCLC Sciences, LLCXiaolian Gao PhD Christoph Eicken PhD2575 W. Bellfort, Suite 270, Houston, TX 77054 Xiaolian Gao, PhD Christoph Eicken, PhDXi h Zh PhD Ch i H b l
, , ,Tel 713 664-7087 Fax 713 664-8181 Xiaochuan Zhou, PhD Chris Hebel Tel. 713 664-7087, Fax 713 664-8181
Molecular Diagnostics / Biomarkers Identification of specific Drug Discovery / Therapeutics Identification of miRNAsMolecular Diagnostics / Biomarkers – Identification of specific Drug Discovery / Therapeutics – Identification of miRNAs g / p
iRNA iRNA i b d i t th t t bi k
g y / pth t l ti l l i di t t d ibl th timiRNAs or miRNA expression based signatures that can act as biomarkers that play essential roles in disease to act as drugs or possible therapeutic p g
f i di / th l ip y g p p
t t i hibitfor various diseases/pathologies. targets inhibitors. /p g g
1 Make accurate and detailed clinical diagnosis 1 miRNAs as tumor suppressor drugs1. Make accurate and detailed clinical diagnosis 1. miRNAs as tumor suppressor drugs
2. Determine prognosis and predict treatment efficacy 2. miRNAs as drug targetsp g p y
3 M it d th h lth ff t f i t l d th t i t
g g
3 St d f iRNA t d t d h / di i t3. Monitor and assess the health effects of environmental and other toxicants 3. Study of miRNAs to understand chemo/radio resistance Send Me This PosterDIAGNOSIS TUMOR SUPPRESSORS
Send Me This PosterDIAGNOSIS TUMOR SUPPRESSORS
Identification of a miRNA signature of miRNA expression patterns can distinguish miR‐215 is a tumour suppressor in renal cell Endogenous human miRNAs that suppressIdentification of a miRNA signature of l i h i f i i j
miRNA expression patterns can distinguish b l ll i b
miR‐215 is a tumour suppressor in renal cell i i
Endogenous human miRNAs that suppress b irenal ischemia reperfusion injury between renal cell carcinoma subtypes carcinoma metastasis breast cancer metastasisp j y yp
Renal ischemia f
Renal cell carcinoma (RCC) d ff
Renal cell carcinoma (RCC) h
Although metastasis is h h lreperfusion injury
(IRI) i i t dencompasses different hi t l i bt
is the most common l f th d lt
the overwhelming cause f t lit i ti t(IRI) is associated
with significanthistologic subtypes. Distinguishing between
neoplasm of the adult kidney Metastatic RCC is
of mortality in patients with solid tumours ourwith significant
morbidity andDistinguishing between the subtypes is usually
kidney. Metastatic RCC is difficult to treat The 5‐
with solid tumours, our understanding of itsmorbidity and
mortalitythe subtypes is usually made by morphologic
difficult to treat. The 5‐year survival rate for
understanding of its molecular and cellularmortality. made by morphologic
assessment, which is notyear survival rate for metastatic RCC is ≤10%.
molecular and cellular determinants is limited.
miRNA expression assessment, which is not always accurate.
metastatic RCC is ≤10%. determinants is limited.p
profiling conducted y
Performed a miRNA Microarray based miRNA on RNA prepared A total of 94 different microarray to identify a profiling of highly from IRI, sham, and
k d fsubtype cases were
l dmiRNA signature h f
metastatic human breast ll dnaive kidneys of mice
l d ianalyzed. miRNA i l i
characteristic of t t ti d ith
cancer cell derivatives h i ld d t frevealed nine
miRNAs that aremicroarray analysis was performed on fresh frozen
metastatic compared with primary RCCs and
has yielded a set of miRNAs for whichmiRNAs that are
differentiallyperformed on fresh frozen tissues of three common
primary RCCs and validated results by qRT‐
miRNAs for which expression is specificallydifferentially
expressed followingtissues of three common RCC subtypes (clear cell
validated results by qRT‐PCR Identified miR‐215 as
expression is specifically lost as human breastexpressed following
IRI when comparedRCC subtypes (clear cell, chromophobe, and
PCR. Identified miR 215 as significant and performed
lost as human breast cancer cells developIRI when compared
with sham controls. chromophobe, and papillary) and on
significant and performed experimental and
cancer cells develop metastatic potential.
Fig 1 ‐miR‐126 suppresses overall tumour growth and lif ti h iR 335 d iR 206 l t
p p y)oncocytoma. Results were
pbioinformatic analyses to
pproliferation whereas miR‐335 and miR‐206 regulate migration and morphology (A) Tumour volumes in
The differentially validated on the original explore the involvement Results show that migration and morphology. (A) Tumour volumes in LM2 cells expressing individual miRNAs or the control
expressed miRNAs ld b l d
as well as on an d d f
Fig 1 ‐ A hierarchic cluster heat map showing diff ti l iRNA i i l kid
Fig 1 ‐ Identification of a miRNA signature following renal IRI. of miR‐215 in RCC d
restoring the expression f h
p ghairpin measured over time. (B) Viable cells in LM2 or
could be placed into f b d
independent set of t i RT PCR
differential miRNA expression in normal kidney, oncocytoma and different RCC subtypes
(A) Heat map of miRNAs differentially expressed in the kidneys f i ft IRI h ti (B) Pl t f b
progression and t t i
Fig 1 ‐miR‐215 has a negative effect on cellularof these miRNAs in
li t llprimary breast cancer line CN34‐BoM1 expressing miR‐126 iR 335 iR 206 d t l ll (C) P t lfour groups based on
their expressiontumours, using qRT‐PCR analysis with miRNA
oncocytoma, and different RCC subtypes.
The clustering of the different sample types byof mice after IRI or sham operation. (B) Plots of above microarray data expressed as the mean signal intensity ± SE
metastasis.Fig 1 miR 215 has a negative effect on cellular migration and invasion. (A) Representative
malignant cells suppresses lung and
126, miR‐335 or miR‐206 and control cells (C) Parental MDA‐MB‐231 cells and lung metastatic LM2 cellstheir expression
patterns Theseanalysis with miRNA specific primers
The clustering of the different sample types by expression pattern is clear.
microarray data expressed as the mean signal intensity ± SE.
The differentially expressed miRNAs could be placed into four Results show that miR‐215photomicrographs (B) Cell migration (C) Cells
f d i h i 21 h d d d ll l
suppresses lung and bone metastasis by
MDA MB 231 cells and lung metastatic LM2 cells stained with the actin marker phalloidin. (D) Trans‐well patterns. These
findings define aspecific primers. p pThe differentially expressed miRNAs could be placed into four
groups based on their expression patterns following IRI: group 1Results show that miR‐215 can affect metastatic
transfected with miR‐215 showed decreased cellular invasion after 22 h (D) Decreased protein expression
bone metastasis by human cancer cells in
p ( )migration of LM2 and CN34‐BoM1 cells transduced with
findings define a molecular fingerprint Developed a classification
groups based on their expression patterns following IRI: group 1 was rapidly up‐regulated, group 2 also up‐regulated, group 3
can affect metastatic potential and
invasion after 22 h. (D) Decreased protein expression in cells that were transfected with miR‐215.
human cancer cells in vivo. miR‐126 restoration
miRNAs or a control hairpin. molecular fingerprint of renal injury.
Developed a classification system that can YM Youssef, N White, J Grigull, A Krizova, C Samy et
was rapidly down‐regulated, group 4 was also down‐regulated.potential and demonstrate that
in cells that were transfected with miR 215. vivo. miR 126 restoration reduces overall tumour j y y
distinguish the different , , g , , y
al. (2011) Accurate Molecular Classification of Kidney Cancer Subtypes Using MicroRNA overexpression of miR‐215
Whit NM Kh ll HW G i ll J Ad i S Y f YM Hgrowth and proliferation,
Godwin JG, Ge X, Stephan K, Jurisch A, Tullius SG, Iacomini J. ( )
RCC subtypes using y yp g
Signature. European Urology 59(5), 721‐30. decreased cellular White NM, Khella HW, Grigull J, Adzovic S, Youssef YM, Honey RJ, Stewart R, Pace KT, Bjarnason GA, Jewett MA, Evans AJ, G b il M Y f GM (2011) iRNA fili i t t ti
whereas miR‐335 inhibits Tavazoie SF, Alarcón C, Oskarsson T, Padua D, Wang Q, Bos PD, Gerald WL M é J (2008) E d h i RNA th t(2010) Identification of a microRNA signature of renal
ischemia reperfusion injury. Proc Natl Acad Sci USA 107(32), unique miRNA signatures. migration and invasion in ll l d l
Gabril M, Yousef GM. (2011) miRNA profiling in metastatic renal cell carcinoma reveals a tumour‐suppressor effect for iR 215 B J C 105(11) 1741 49
metastatic cell invasion. WL, Massagué J. (2008) Endogenous human microRNAs that suppress breast cancer metastasis. Nature 451(7175), 147‐52
14339‐44. an RCC cell line model. miR‐215. Br J Cancer 105(11), 1741‐49..
PROGNOSIS DRUG TARGETSPROGNOSIS DRUG TARGETS
miRNA profiling of plasma may provide a miR‐150 as a potential biomarker associated Modulating miR‐21 expression via antisense‐ Downregulation of miRNA‐29 by antisensemiRNA profiling of plasma may provide a l l i f i
miR‐150 as a potential biomarker associated i h i d h i i
Modulating miR‐21 expression via antisense‐di d d l i (k kd ) h d i ifi
Downregulation of miRNA‐29 by antisense i hibi i di lmolecular signature for tumor aggressiveness with prognosis and therapeutic outcome in mediated depletion (knockdown) had a significant inhibitors protects against myocardial g gg
in pancreatic cancerp g p
colorectal cancerp ( ) g
negative effect on cardiomyocyte hypertrophyp g y
ischaemia‐reperfusion injuryin pancreatic cancer colorectal cancer negative effect on cardiomyocyte hypertrophy. ischaemia‐reperfusion injury
Pancreatic cancer (PC) has the ll i l
Up to 90% of patients with l l (CRC)
Using microarray analysis, d d h
Pioglitazone (PIO), a i lifpoorest overall survival rate
ll hcolorectal cancer (CRC) can b d b if th
we demonstrated that iRNA b tl
peroxisome proliferator‐ti t d t (PPAR)among all human cancers
because of late diagnosis andbe cured by surgery if the disease is detected at an
miRNAs are aberrantly expressed in hypertrophic
activated receptor (PPAR)‐γ agonist protects againstbecause of late diagnosis and
absence of screening toolsdisease is detected at an early stage However it is
expressed in hypertrophic mouse hearts miR‐21 was
agonist, protects against myocardial ischaemia–absence of screening tools. early stage. However, it is
often diagnosed only at anmouse hearts. miR‐21 was significantly dysregulated
myocardial ischaemiareperfusion (IR) injury.
Compared the expression profile often diagnosed only at an advanced stage and the
significantly dysregulated (more than fourfold
reperfusion (IR) injury. p p p
of miRNAs in the plasma of g
prognosis is therefore poor.(increase) when compared Evaluated the expression
patients diagnosed with PC with the sham surgical changes of miRNAs in the (n=50) with healthy volunteers Performed global analysis of group. rat heart after PIO (n=10). 37 iRNA d l d
miRNA expression profiles of l l l i A iR 21 i hibi 2’OM
administration using iRNA d f d37 miRNAs down‐regulated
54 iRNA l t dnormal colorectal tissues, l t l d ti
A miR‐21 inhibitor, 2’OMe‐iR 21 d d iR 21
miRNA arrays and found th t iR 29 d l l54 miRNAs up‐regulated colorectal adenoma tissues
and CRC tissues by miRNAmiR‐21, decreased miR‐21 levels and inhibited myocyte
that miR‐29a and c levels decreased remarkably after
• Expression of miR‐21 wasand CRC tissues by miRNA microarray
levels and inhibited myocyte hypertrophy stimulated by
decreased remarkably after 7‐day treatment with PIOExpression of miR‐21 was
correlated with worse survivalmicroarray. hypertrophy stimulated by
either Ang II or PE. In7‐day treatment with PIO.
correlated with worse survival • Expression of let‐7 was miR‐150 expression
either Ang II or PE. In contrast, control oligos Antagomirs against miR‐
Fig 1 – miRNA expression and survival (A) Box plot ti th i f iRNA
pinversely correlated with
pdecreased with the transition
, g(2’OMe‐EGFP) had no effect
g g29a or ‐29c significantly
representing the expression of seven miRNAs as assessed by qRT‐PCR (B) Kaplan‐Meier curves and
survival from normal mucosa to CRC on miR‐21 expression and reduced myocardial infarct assessed by qRT PCR. (B) Kaplan Meier curves and log‐rank tests for miR‐21 expression and patient
• miR‐21 family was markedly in parallel with increasing Fi 1 E i l l f iR 150 i l l
cell hypertrophy. size and apoptosis in hearts g p p
survival. (C) Kaplan‐Meier curves and log‐rank tests
over‐expressed in chemo‐i PC ll li
carcinogenesis of the l l i
Fig 1 ‐ Expression levels of miR‐150 in colorectal cancer (CRC) adenoma and normal colorectal tissue (A) (B) µParaflo R l h iRNA
subjected to IR injury. for let‐7d expression and patient survival.
resistant PC cell lines colorectal tissue. (CRC), adenoma and normal colorectal tissue. (A) (B) µParaflo miRNA microarray assay showed that the expression of miR‐
Results suggest that miRNAs i l d i di Th fi di h th t
Fig 1 ‐ (A) Relative expression of miR‐29a 16 h after the thi d i j ti f t i ( t 29 ) i
These results suggest that higher expression of iR 21 ld bi k f
Results suggest that identifying Found that the miR 150
c oa ay assay s o ed t at t e e p ess o o150 levels in normal colorectal tissue, adenoma tissue and
are involved in cardiac hypertrophy formation Fig 1 ‐ The effect of miR‐21 inhibitor 2OMe‐miR‐21 on
These finding show that modulation of miRNAs can
third injection of antagomir (anta‐29a) or missense antagomir (misanta‐29) (B) Relative expression of miR‐29c
miR‐21 could serve as a biomarker for worse survival of PC patients and thus could serves as anResults suggest that identifying
and validating the expression ofFound that the miR‐150 expression status of patients
CRC tissue decreased with the progression of carcinogenesis f l l l i d i CRC (C) A
hypertrophy formation. miRNAs might be a new
Fig 1 The effect of miR 21 inhibitor 2OMe miR 21 on miR‐21 expression in cultured cardiac myocytes with
modulation of miRNAs can be achieved by
antagomir (misanta 29). (B) Relative expression of miR 29c 16 h after the third injection. (C) Effect of anta‐29a, anta‐
survival of PC patients, and thus could serves as an important prognostic marker.and validating the expression of
miRNAs in newly diagnosedexpression status of patients with CRC is associated with
from normal colorectal tissue to adenoma tissue to CRC. (C) A validation experiment was carried out using quantitative
miRNAs might be a new therapeutic target for
hypertrophy. (A) Transfection of miR‐21 inhibitor (2’OM iR 21) d l li (2’OM EGFP)
be achieved by pharmacological
j ( ) ,29c, and misanta‐29 on myocardial IS. (D) % of TUNEL‐
p p g
miRNAs in newly diagnosed patients could serve as potential
with CRC is associated with survival and response to
validation experiment was carried out using quantitative reverse transcription PCR (qRT‐PCR) which also showed that
therapeutic target for cardiovascular diseases
(2’OMe‐miR‐21) and control oligo (2’OMe‐EGFP) labeled with a fluorescent dye (red color) into the
pharmacological intervention and provide a
positive‐stained cardiomyocytes in the ischaemic area of t i t t d i h t bj t d t IR (E)
p pbiomarker for tumor
padjuvant chemotherapy is
e e se t a sc pt o C (q C ) c a so s o ed t atthe expression of miR‐150 decreased with the transition from involving cardiac
labeled with a fluorescent dye (red color) into the cultured cardiac myocytes. (B) The effects of miR‐21
prationale for the
antagomir‐pre‐treated mice hearts subjected to IR. (E) Representative staining pattern Arrows indicate TUNEL‐
aggressiveness, and such miRNAs Ali S, Almhanna K, Chen W, Philip PA, Sarkar FH. (2010) therefore a potential normal mucosa via adenoma tissue to CRC tissue. hypertrophy such as cultured cardiac myocytes. (B) The effects of miR 21 inhibitor on the expression levels of miR‐21 in cultured development of miRNA‐
Representative staining pattern. Arrows indicate TUNELpositive nuclei which are stained blue.
could be useful for the screening Differentially expressed miRNAs in the plasma may provide a molecular signature for aggressive pancreatic cancer. Am J
( )
biomarker associated with M Y Zh P W F Zh H Y J P J Li W
hypertension, ischemic heart cardiac myocytes with hypertrophy. based strategies for the p
of high‐risk patients. Transl Res 3(1), 28‐47. the prognosis and h i i CRC
Ma Y, Zhang P, Wang F, Zhang H, Yang J, Peng J, Liu W, Qin H. (2011) miR‐150 as a potential biomarker
i t d ith i d th ti t i
disease, valvular diseases, d d i di d
Cheng Y, Ji R, Yue J, Yang J, Liu X, Chen H, Dean DB, Zhang C. (2007)attenuation of IR injury. Ye Y, Hu Z, Lin Y, Zhang C, Perez‐Polo JR. (2010)
Downregulation of microRNA‐29 by antisense inhibitorstherapeutic outcome in CRC. associated with prognosis and therapeutic outcome in
colorectal cancer. Gut [Epub ahead of print]. and endocrine disorders.
Cheng Y, Ji R, Yue J, Yang J, Liu X, Chen H, Dean DB, Zhang C. (2007) MicroRNAs Are Aberrantly Expressed in Hypertrophic Heart. Do They Play a Role in Cardiac Hypertrophy? Am J Pathol 170(6), 1831‐40.
Downregulation of microRNA 29 by antisense inhibitors and a PPAR‐{gamma} agonist protects against myocardial ischaemia‐reperfusion injury. Cardiovasc Res 87(3), 535‐44.Play a Role in Cardiac Hypertrophy? Am J Pathol 170(6), 1831 40. ischaemia reperfusion injury. Cardiovasc Res 87(3), 535 44.
TOXICITY RESISTANCE
i i fil di i i h h i i b d bi k f h fi di id h i i i l h i
TOXICITY RESISTANCE
miRNA expression profiles distinguish the miRNAs expression can be used as biomarkers of The first direct evidence that miRNAs can Restoring miR‐342 ‐ a novel therapeutic p p gcarcinogenic effects of riddelliine in rat liver
pchemical exposure in risk assessment of chemical suppress resistance to anticancer cytotoxic
g papproach to sensitizing and suppressing thecarcinogenic effects of riddelliine in rat liver chemical exposure in risk assessment of chemical
i isuppress resistance to anticancer cytotoxic h
approach to sensitizing and suppressing the h f if i bcarcinogenesis therapy growth of tamoxifen resistant breast tumors
A l d iRNA i filP li idi lk l id (PA )
g py
T ll i i
g
T i h l iAnalyzed miRNA expression profiles of human bronchial epithelial (HBE)
Pyrrolizidine alkaloids (PAs) are the most common
Tumor cells use preexisting prosurvival signaling pathways to
Tumor resistance to the selective estrogen receptor modulatorof human bronchial epithelial (HBE)
cells expressing an oncogenic alleleare the most common plant constituents that
prosurvival signaling pathways to evade the damaging and cytotoxic
estrogen receptor modulator tamoxifen remains a seriouscells expressing an oncogenic allele
of H‐Ras (HBER) at different stages ofplant constituents that poison livestock wildlife
evade the damaging and cytotoxic effects of anticancer agents
tamoxifen remains a serious clinical problem especially inof H Ras (HBER) at different stages of
transformation induced bypoison livestock, wildlife and humans. Riddelliine is
effects of anticancer agents. Radiation therapy is a primary form
clinical problem especially in patients with tumors that alsotransformation induced by
benzo(a)pyrene (BaP) by miRNA and humans. Riddelliine is a genotoxic PA.
Radiation therapy is a primary form of cytotoxic anticancer treatment,
patients with tumors that also overexpress HER2. However, a ( )py ( ) y
array. g y ,
but agents that successfully modify p ,
unifying molecular mechanism of Analysis with microarrays the radiation response in vivo are tamoxifen resistance has remained
Revealed 12 miRNAs differentially showed that the miRNA lacking. elusive.expressed in HBER cells at both pre‐
f d d f dexpression profiles were l l l ifi d i iRNA i d h A l d l i l ll d l ftransformed and transformed stages.
The expression of miR 638 in HBERclearly classified into two groups riddelliine
miRNA microarrays compared the relative levels of cellular miRNAs
Analyzed multiple cell models of tamoxifen resistance derived fromThe expression of miR‐638 in HBER
cells increased upon treatment ofgroups, riddelliine treatment versus other
relative levels of cellular miRNAs before and after radiation Found
tamoxifen resistance derived from MCF 7 cells to examine thecells increased upon treatment of
BaP in a dose‐dependent mannertreatment versus other samples 47 miRNAs were Fig 1 ‐ PCA and HCA of miRNA expression levels in
before and after radiation. Found that the let‐7 family of miRNAs is
MCF‐7 cells to examine the influence of miRNAs on tamoxifenBaP in a dose dependent manner. samples. 47 miRNAs were
significantly dysregulatedFig 1 PCA and HCA of miRNA expression levels in rat liver samples from riddelliine, aristolochic acid
that the let 7 family of miRNAs is overrepresented in a class of
influence of miRNAs on tamoxifen resistance. Observed significant
The expression of miR‐638 was also significantly dysregulated by riddelliine treatment.
p ,and control treatments showing the global effects
overrepresented in a class of miRNAs exhibiting altered Fig 1 ‐ Restored miR‐342 expression sensitizes
resistance. Observed significant and dramatic downregulation of p
examined in peripheral lymphocytes y
of chemical treatment on miRNA expression in rat li
gexpression in response to radiation.
Fig 1 Restored miR 342 expression sensitizes resistant cells to tamoxifen. Tamoxifen
gmiR‐342 in tamoxifen resistant
from 86 polycyclic aromatic Results suggest that liver.
Fig 1 ‐ Dose‐dependent and time course of Created a radiosensitive state by resistant cell lines were transfected with f i l 20 f
MCF‐7 variant cell lines. Restoring hydrocarbons (PAHs)‐exposed (PE) miRNAs actively respond to (A) The principal component analysis (PCA). The red,
Fig 1 Dose dependent and time course of miR‐638 expression in HBER cells treated overexpressing the select let‐7 transfection reagent alone, 20 nM of
scrambled precursor negative control (miRmiR‐342 expression in the cell
workers. The average expression l l f iR 638 i i h l
a mutagenic dose of idd llii d h
( ) p p p y ( ) ,purple and blue circles denote the samples from with BaP. The fold changes of miR‐638
i l l l i h l
family of miRNAs in vitro in lung ll h d i
scrambled precursor negative control (miR‐NC), or 20 nM of miR‐342‐3p precursor (miR‐
lines sensitized these cells to if i d d i i hlevel of miR‐638 in peripheral
lymphocytes from 86 PE workersriddelliine and the pattern of miRNA expression has
riddelliine, and control treatments, respectively. (B) Th hi h l l t i l i (HCA) Th
expression levels relative to the control (DMSO) in HBER cells (A) or HBE cells (C) after
cancer cells, whereas decreasing their levels causes radioresistance
NC), or 20 nM of miR 342 3p precursor (miR342). At 24 hr post‐transfection cells were
tamoxifen‐induced apoptosis with a dramatic reduction in celllymphocytes from 86 PE workers
increased by 72% compared withof miRNA expression has the potential to be used as
The hierarchal clustering analysis (HCA). The riddelliine samples clearly cluster together
(DMSO) in HBER cells (A) or HBE cells (C) after treated with BaP. miR‐638 expression was
their levels causes radioresistance.
Fi 1 R l ti l l f th l t 7 f il iRNAtreated for 96 hr with 100 pM of E2 alone or i bi i i h 1 0 ( )
a dramatic reduction in cell growthincreased by 72% compared with
control groupthe potential to be used as a biomarker of genotoxicity
riddelliine samples clearly cluster together. treated with BaP. miR 638 expression was also detected in HBER (B) or HBE (D) cells These findings are the first direct
Fig 1 ‐ Relative levels of the let‐7 family miRNAs change significantly over time after irradiation
in combination with 1.0 μM TAM. (A) MTT assay was used to measure proliferation as a
growth. control group. a biomarker of genotoxicity
and carcinogenicity fortreated with BaP.
These findings are the first direct evidence that miRNAs can suppress
change significantly over time after irradiation. (A) Microarray expression results of irradiated
assay was used to measure proliferation as a function of metabolism, (B) apoptosis wasThese findings suggest that miR‐
The upregulation of miR‐638 in PE and carcinogenicity for riddelliine and possibly
evidence that miRNAs can suppress resistance to anticancer cytotoxic
( ) y pA549 cells. (B) Expression of let‐7 miRNAs in an
function of metabolism, (B) apoptosis was assayed by cell death ELISA, or (C) cells were
These findings suggest that miR342 regulates tamoxifen response p g
workers, which leads to an inhibition ( )
p yother PAs.
Li D et al (2011) Aberrant Expression of miR 638 Contributes to
ytherapy, a common feature of irradiated normal lung epithelial line, CRL2741.
(C) R l ti PCR ltstained with DAPI and propidium iodide (PI).
g pin breast tumor cell lines and our
of the cellular repair system, Chen T, Li Z, Yan J, Yang X, Salminen W. (2011) MicroRNA expression profiles distinguish the carcinogenic effects of
( )
Li D et al. (2011) Aberrant Expression of miR‐638 Contributes to Benzo(a)pyrene‐induced Human Cell Transformation. Toxicol Sci 125(2) 382 91
cancer cells, and suggest that (C) Real‐time PCR results. clinical data indicates a trend indicates that miR‐638 is a good riddelliine in rat liver. Mutagenesis 27(1), 59‐66. 125(2),382‐91.
miRNAs may be a viable tool to Weidhaas JB, Babar I, Nallur SM, Trang P, Roush S, Boehm M, Gillespie E,
Cittelly DM, Das PM, Spoelstra NS, Edgerton SM, Richer JK, Thor AD, Jones FE. (2010) Downregulation of miR‐342 is
towards reduced miR‐342 biomarker for evaluation of
i l h i laugment current cancer therapies. Slack FJ. (2007) MicroRNAs as potential agents to alter resistance to
cytotoxic anticancer therapy. Cancer Res 67(23), 11111‐16. Associated with Tamoxifen Resistant Breast Tumors. Mol Cancer 9(1), 317.
expression and tamoxifen ienvironmental chemical exposure. resistance.
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