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Let-7 repression leads to HMGA2 overexpression in uterine leiomyosarcoma.

Shi G, Perle MA, Mittal K, Chen H, Zou X, Narita M, Hernando E, Lee P, Wei JJ - J. Cell. Mol. Med. (2008)

Bottom Line: To test whether HMGA2 and let-7s play a role in ULMS, we examined the levels of endogenous HMGA2 and let-7 expression and found a significant correlation between these two molecules in a case-matched cohort of human ULMS.We found that overexpression of HMGA2 and let-7-mediated HMGA2 repression is a relevant molecular alteration in ULMS.Disrupting the control of HMGA2 and let-7 pairs promotes ULMS cell growth in vitro.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.

ABSTRACT
Overexpression of HMGA2 is common in uterine leiomyomas (ULM). The expression of HMGA2 in its malignant counterpart - uterine leiomyosarcomas (ULMS) remains undetermined. Recently it has been shown that repression of HMGA2 by microRNA let-7s is a critical molecular regulatory mechanism associated with tumour growth in many tumours and cell types, including leiomyomas. To test whether HMGA2 and let-7s play a role in ULMS, we examined the levels of endogenous HMGA2 and let-7 expression and found a significant correlation between these two molecules in a case-matched cohort of human ULMS. We found that overexpression of HMGA2 and let-7-mediated HMGA2 repression is a relevant molecular alteration in ULMS. Disrupting the control of HMGA2 and let-7 pairs promotes ULMS cell growth in vitro.

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Related in: MedlinePlus

Semi-quantitative RT-PCR (upper panel) and Western blot (lower panel) analyses of HMGA2 and some let-7 family members in fresh frozen tissue samples of five ULMS. (A) HMGA2 mRNA was detectable in all 5 ULMS. One matched myometrium (MM) and one leiomyoma (ULM) were used as HMGA2 negative and positive control, respectively. Actin was used as loading control. Among let-7 members, let-7c was relatively higher than others in all ULMS. U6 was used as small RNA loading control. Western blot analysis of HMGA2 was examined in 4 ULMS (bottom). (B) Photographs illustrate gross appearance of a ULMS cross-section in case ULMS-34 and the corresponding karyotype (inserts with chromosome alterations) obtained in two different tumour regions.
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fig02: Semi-quantitative RT-PCR (upper panel) and Western blot (lower panel) analyses of HMGA2 and some let-7 family members in fresh frozen tissue samples of five ULMS. (A) HMGA2 mRNA was detectable in all 5 ULMS. One matched myometrium (MM) and one leiomyoma (ULM) were used as HMGA2 negative and positive control, respectively. Actin was used as loading control. Among let-7 members, let-7c was relatively higher than others in all ULMS. U6 was used as small RNA loading control. Western blot analysis of HMGA2 was examined in 4 ULMS (bottom). (B) Photographs illustrate gross appearance of a ULMS cross-section in case ULMS-34 and the corresponding karyotype (inserts with chromosome alterations) obtained in two different tumour regions.

Mentions: Karyotype: t(12; 14) and tri(12) (see Fig. 2); IHC: immunohistochemistry; ISH: in situ hybridization.


Let-7 repression leads to HMGA2 overexpression in uterine leiomyosarcoma.

Shi G, Perle MA, Mittal K, Chen H, Zou X, Narita M, Hernando E, Lee P, Wei JJ - J. Cell. Mol. Med. (2008)

Semi-quantitative RT-PCR (upper panel) and Western blot (lower panel) analyses of HMGA2 and some let-7 family members in fresh frozen tissue samples of five ULMS. (A) HMGA2 mRNA was detectable in all 5 ULMS. One matched myometrium (MM) and one leiomyoma (ULM) were used as HMGA2 negative and positive control, respectively. Actin was used as loading control. Among let-7 members, let-7c was relatively higher than others in all ULMS. U6 was used as small RNA loading control. Western blot analysis of HMGA2 was examined in 4 ULMS (bottom). (B) Photographs illustrate gross appearance of a ULMS cross-section in case ULMS-34 and the corresponding karyotype (inserts with chromosome alterations) obtained in two different tumour regions.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4516537&req=5

fig02: Semi-quantitative RT-PCR (upper panel) and Western blot (lower panel) analyses of HMGA2 and some let-7 family members in fresh frozen tissue samples of five ULMS. (A) HMGA2 mRNA was detectable in all 5 ULMS. One matched myometrium (MM) and one leiomyoma (ULM) were used as HMGA2 negative and positive control, respectively. Actin was used as loading control. Among let-7 members, let-7c was relatively higher than others in all ULMS. U6 was used as small RNA loading control. Western blot analysis of HMGA2 was examined in 4 ULMS (bottom). (B) Photographs illustrate gross appearance of a ULMS cross-section in case ULMS-34 and the corresponding karyotype (inserts with chromosome alterations) obtained in two different tumour regions.
Mentions: Karyotype: t(12; 14) and tri(12) (see Fig. 2); IHC: immunohistochemistry; ISH: in situ hybridization.

Bottom Line: To test whether HMGA2 and let-7s play a role in ULMS, we examined the levels of endogenous HMGA2 and let-7 expression and found a significant correlation between these two molecules in a case-matched cohort of human ULMS.We found that overexpression of HMGA2 and let-7-mediated HMGA2 repression is a relevant molecular alteration in ULMS.Disrupting the control of HMGA2 and let-7 pairs promotes ULMS cell growth in vitro.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.

ABSTRACT
Overexpression of HMGA2 is common in uterine leiomyomas (ULM). The expression of HMGA2 in its malignant counterpart - uterine leiomyosarcomas (ULMS) remains undetermined. Recently it has been shown that repression of HMGA2 by microRNA let-7s is a critical molecular regulatory mechanism associated with tumour growth in many tumours and cell types, including leiomyomas. To test whether HMGA2 and let-7s play a role in ULMS, we examined the levels of endogenous HMGA2 and let-7 expression and found a significant correlation between these two molecules in a case-matched cohort of human ULMS. We found that overexpression of HMGA2 and let-7-mediated HMGA2 repression is a relevant molecular alteration in ULMS. Disrupting the control of HMGA2 and let-7 pairs promotes ULMS cell growth in vitro.

Show MeSH
Related in: MedlinePlus