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Tumor suppressive microRNA-137 negatively regulates Musashi-1 and colorectal cancer progression.

Smith AR, Marquez RT, Tsao WC, Pathak S, Roy A, Ping J, Wilkerson B, Lan L, Meng W, Neufeld KL, Sun XF, Xu L - Oncotarget (2015)

Bottom Line: MicroRNA miR-137 was identified as a MSI1-targeting microRNA by immunoblotting and luciferase reporter assays.In addition to reduced MSI1 protein, exogenous expression of miR-137 inhibited cell growth, colony formation, and tumorsphere growth of colon cancer cells.Finally, in vivo studies demonstrated that induction of miR-137 can decrease growth of human colon cancer xenografts.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biosciences, University of Kansas, Lawrence, KS, USA.

ABSTRACT
Stem cell marker, Musashi-1 (MSI1) is over-expressed in many cancer types; however the molecular mechanisms involved in MSI1 over-expression are not well understood. We investigated the microRNA (miRNA) regulation of MSI1 and the implications this regulation plays in colorectal cancer. MicroRNA miR-137 was identified as a MSI1-targeting microRNA by immunoblotting and luciferase reporter assays. MSI1 protein was found to be highly expressed in 79% of primary rectal tumors (n=146), while miR-137 expression was decreased in 84% of the rectal tumor tissues (n=68) compared to paired normal mucosal samples. In addition to reduced MSI1 protein, exogenous expression of miR-137 inhibited cell growth, colony formation, and tumorsphere growth of colon cancer cells. Finally, in vivo studies demonstrated that induction of miR-137 can decrease growth of human colon cancer xenografts. Our results demonstrate that miR-137 acts as a tumor-suppressive miRNA in colorectal cancers and negatively regulates oncogenic MSI1.

No MeSH data available.


Related in: MedlinePlus

Working modelRNA binding protein and stem cell regulator, MSI1, positively regulates the Wnt and Notch signaling pathways by binding to and inhibiting the translation of target mRNA; APC, p21WAF-1, and NUMB. In this study, we show that miR-137 acts as a tumor suppressive microRNA, in part by negatively regulating MSI1 and subsequently Wnt and Notch signaling pathways.
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Figure 7: Working modelRNA binding protein and stem cell regulator, MSI1, positively regulates the Wnt and Notch signaling pathways by binding to and inhibiting the translation of target mRNA; APC, p21WAF-1, and NUMB. In this study, we show that miR-137 acts as a tumor suppressive microRNA, in part by negatively regulating MSI1 and subsequently Wnt and Notch signaling pathways.

Mentions: Overall, we describe an important tumor-suppressive mechanism of miR-137 through the negative regulation of MSI1 and Notch/Wnt signaling, outlined in our working model (Figure 7). miR-137 is a promising candidate for future miRNA-based molecular therapy for treating a variety of cancer types, including colorectal cancer. Our findings provide insight into the mechanism of dysregulation of colon cancer stem cells and eventually colorectal cancer initiation and progression. By understanding the molecular mechanisms of colorectal cancer biology, therapies may be developed to better combat this deadly disease.


Tumor suppressive microRNA-137 negatively regulates Musashi-1 and colorectal cancer progression.

Smith AR, Marquez RT, Tsao WC, Pathak S, Roy A, Ping J, Wilkerson B, Lan L, Meng W, Neufeld KL, Sun XF, Xu L - Oncotarget (2015)

Working modelRNA binding protein and stem cell regulator, MSI1, positively regulates the Wnt and Notch signaling pathways by binding to and inhibiting the translation of target mRNA; APC, p21WAF-1, and NUMB. In this study, we show that miR-137 acts as a tumor suppressive microRNA, in part by negatively regulating MSI1 and subsequently Wnt and Notch signaling pathways.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494958&req=5

Figure 7: Working modelRNA binding protein and stem cell regulator, MSI1, positively regulates the Wnt and Notch signaling pathways by binding to and inhibiting the translation of target mRNA; APC, p21WAF-1, and NUMB. In this study, we show that miR-137 acts as a tumor suppressive microRNA, in part by negatively regulating MSI1 and subsequently Wnt and Notch signaling pathways.
Mentions: Overall, we describe an important tumor-suppressive mechanism of miR-137 through the negative regulation of MSI1 and Notch/Wnt signaling, outlined in our working model (Figure 7). miR-137 is a promising candidate for future miRNA-based molecular therapy for treating a variety of cancer types, including colorectal cancer. Our findings provide insight into the mechanism of dysregulation of colon cancer stem cells and eventually colorectal cancer initiation and progression. By understanding the molecular mechanisms of colorectal cancer biology, therapies may be developed to better combat this deadly disease.

Bottom Line: MicroRNA miR-137 was identified as a MSI1-targeting microRNA by immunoblotting and luciferase reporter assays.In addition to reduced MSI1 protein, exogenous expression of miR-137 inhibited cell growth, colony formation, and tumorsphere growth of colon cancer cells.Finally, in vivo studies demonstrated that induction of miR-137 can decrease growth of human colon cancer xenografts.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biosciences, University of Kansas, Lawrence, KS, USA.

ABSTRACT
Stem cell marker, Musashi-1 (MSI1) is over-expressed in many cancer types; however the molecular mechanisms involved in MSI1 over-expression are not well understood. We investigated the microRNA (miRNA) regulation of MSI1 and the implications this regulation plays in colorectal cancer. MicroRNA miR-137 was identified as a MSI1-targeting microRNA by immunoblotting and luciferase reporter assays. MSI1 protein was found to be highly expressed in 79% of primary rectal tumors (n=146), while miR-137 expression was decreased in 84% of the rectal tumor tissues (n=68) compared to paired normal mucosal samples. In addition to reduced MSI1 protein, exogenous expression of miR-137 inhibited cell growth, colony formation, and tumorsphere growth of colon cancer cells. Finally, in vivo studies demonstrated that induction of miR-137 can decrease growth of human colon cancer xenografts. Our results demonstrate that miR-137 acts as a tumor-suppressive miRNA in colorectal cancers and negatively regulates oncogenic MSI1.

No MeSH data available.


Related in: MedlinePlus