Page 147 - 2014 Printable Abstract Book
P. 147
evidence that external and internal exposure affect to CVD mortality was found. Risk estimates in relation
to external exposure overall agreed with results of our previous study and other large-scale studies.
However, ERR/Gy estimates for CVD incidence in relation to external exposure was higher than that
obtained in Japanese a-bomb survivors.
(PS2-19) Suppressive role of ionizing radiation-induced miR-29c in liver carcinogenesis via targeting
1
1
1
1
Cdk2. Bo Wang, PhD ; Dongping Li, PhD ; Corinne Sidler, PhD ; Natasha Singh, PhD ; Roderick T. Bronson,
2
1
PhD ; and Olga Kovalchuk, PhD, 1 University of lethbridge, Lethbridge, Canada and The Dana
2
Farber/Harvard Comprehensive Cancer Center, Boston, MA
Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death
worldwide and has been linked with radiation. CDK2 plays a key role in cell cycle control, especially the
G1/S transition and progress through S-phase. CDK2 has been demonstrated to be elevated in many
malignancies, including HCC. The underlying mechanisms, however, remain largely unknown. Here, we
show that low-dose IR remarkably induces miR-29c expression in female mouse liver. miR-29c expression
is reduced in liver carcinoma cells, and that is inversely correlated with CDK2 expression. miR-29c
attenuates luciferase activity of a reporter harboring the 3’UTR binding motif of Cdk2 mRNA. Ectopic
expression of miR-29c significantly represses cell proliferation, induces apoptosis and G1 arrest in HB8065,
a human hepatocellular carcinoma cell line used as a model system here. In contrast, knockdown of miR-
29c remarkably enhances HB8065 cell proliferation and suppresses apoptosis, and that are mediated by
upregulation of miR-29c targets BCL2, MCL1, SIRT1, CDK2, and downregulation of phosphorylated p53.
We also find that Skp2 is a direct posttranscriptional target of miR-29c. FISH and immunohistochemical
analyses indicate that miR-29c is downregulated in 50.6%, whereas CDK2 was upregulated in 44% of liver
carcinoma tissues examined. Downregulation of miR-29c contributes significantly to the upregulation of
CDK2 in HCC. Our results suggest that the IR-inducible miR-29c may function as a tumor suppressor that
plays an important role in hepatocellular carcinogenesis via targeting Cdk2, and may represent a target
molecule for therapeutic intervention for this disease.
(PS2-20) Ionizing radiation-inducible miR-27b suppresses leukemia proliferation via targeting cyclin A2.
Dongping Li; Bo Wang; Anna Kovalchuk; and Olga Kovalchuk, university of lethbridge, lethbridge, Canada
Ionizing radiation (IR) is a common and important carcinogen for the development of leukemia.
However, the epigenetic mechanisms underlying remain largely unknown. Here, we showed that IR
triggered the differential expression of miR-27b in mouse thymus tissue in a dose-, time- and gender-
dependent meaner. miR-27b was significantly dwonregulated in leukemia cell lines CCL119 and TIB152.
Interestingly, estrogen receptor alpha (ERα) was overepressed in those two cell lines, and that was
inversely correlated with miR-27b expression. We, therefore, used TIB152 as a model system to determine
the role of ERα in miR-27b expression and the contribution of miR-27b to leukemogenesis. β-Estradiol
caused a rapid and transient reduction in TIB152 cells, and that was inverted by either ERα neutralizing
antibody or ERK1/2 inhibitor. Furthermore, the ectopic miR-27b remarkably suppressed TIB152 cell
proliferation, induced S phase arrest and slight apoptosis. Moreover, the ectopic miR-27b attenuated the
cyclin A2 expression, although it had no effect on the expression of PCNA, PPARγ, CDK2, p21, p27, p-p53,
and cleaved caspase-3. Our data reveal that β-Estradiol may contribute to downregulation of miR-27b in
145 | P a g e
to external exposure overall agreed with results of our previous study and other large-scale studies.
However, ERR/Gy estimates for CVD incidence in relation to external exposure was higher than that
obtained in Japanese a-bomb survivors.
(PS2-19) Suppressive role of ionizing radiation-induced miR-29c in liver carcinogenesis via targeting
1
1
1
1
Cdk2. Bo Wang, PhD ; Dongping Li, PhD ; Corinne Sidler, PhD ; Natasha Singh, PhD ; Roderick T. Bronson,
2
1
PhD ; and Olga Kovalchuk, PhD, 1 University of lethbridge, Lethbridge, Canada and The Dana
2
Farber/Harvard Comprehensive Cancer Center, Boston, MA
Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death
worldwide and has been linked with radiation. CDK2 plays a key role in cell cycle control, especially the
G1/S transition and progress through S-phase. CDK2 has been demonstrated to be elevated in many
malignancies, including HCC. The underlying mechanisms, however, remain largely unknown. Here, we
show that low-dose IR remarkably induces miR-29c expression in female mouse liver. miR-29c expression
is reduced in liver carcinoma cells, and that is inversely correlated with CDK2 expression. miR-29c
attenuates luciferase activity of a reporter harboring the 3’UTR binding motif of Cdk2 mRNA. Ectopic
expression of miR-29c significantly represses cell proliferation, induces apoptosis and G1 arrest in HB8065,
a human hepatocellular carcinoma cell line used as a model system here. In contrast, knockdown of miR-
29c remarkably enhances HB8065 cell proliferation and suppresses apoptosis, and that are mediated by
upregulation of miR-29c targets BCL2, MCL1, SIRT1, CDK2, and downregulation of phosphorylated p53.
We also find that Skp2 is a direct posttranscriptional target of miR-29c. FISH and immunohistochemical
analyses indicate that miR-29c is downregulated in 50.6%, whereas CDK2 was upregulated in 44% of liver
carcinoma tissues examined. Downregulation of miR-29c contributes significantly to the upregulation of
CDK2 in HCC. Our results suggest that the IR-inducible miR-29c may function as a tumor suppressor that
plays an important role in hepatocellular carcinogenesis via targeting Cdk2, and may represent a target
molecule for therapeutic intervention for this disease.
(PS2-20) Ionizing radiation-inducible miR-27b suppresses leukemia proliferation via targeting cyclin A2.
Dongping Li; Bo Wang; Anna Kovalchuk; and Olga Kovalchuk, university of lethbridge, lethbridge, Canada
Ionizing radiation (IR) is a common and important carcinogen for the development of leukemia.
However, the epigenetic mechanisms underlying remain largely unknown. Here, we showed that IR
triggered the differential expression of miR-27b in mouse thymus tissue in a dose-, time- and gender-
dependent meaner. miR-27b was significantly dwonregulated in leukemia cell lines CCL119 and TIB152.
Interestingly, estrogen receptor alpha (ERα) was overepressed in those two cell lines, and that was
inversely correlated with miR-27b expression. We, therefore, used TIB152 as a model system to determine
the role of ERα in miR-27b expression and the contribution of miR-27b to leukemogenesis. β-Estradiol
caused a rapid and transient reduction in TIB152 cells, and that was inverted by either ERα neutralizing
antibody or ERK1/2 inhibitor. Furthermore, the ectopic miR-27b remarkably suppressed TIB152 cell
proliferation, induced S phase arrest and slight apoptosis. Moreover, the ectopic miR-27b attenuated the
cyclin A2 expression, although it had no effect on the expression of PCNA, PPARγ, CDK2, p21, p27, p-p53,
and cleaved caspase-3. Our data reveal that β-Estradiol may contribute to downregulation of miR-27b in
145 | P a g e
