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miR-191 promotes tumorigenesis of human colorectal cancer through targeting C/EBPβ.

Zhang XF, Li KK, Gao L, Li SZ, Chen K, Zhang JB, Wang D, Tu RF, Zhang JX, Tao KX, Wang G, Zhang XD - Oncotarget (2015)

Bottom Line: In this study, we show that miR-191 is highly expressed in colon tumor tissues, and that inhibition of miR-191 leads to decreased cell growth, proliferation and tumorigenicity in a xenograft model.Overexpression of miR-191 in colorectal cancer cell lines alters cell cycle progression and cell resistance to 5-Fu induced cell apoptosis.Mechanistic studies demonstrated that miR-191 directly binds to the 3'UTR of the C/EBPβ mRNA and mediates a decrease in the mRNA and protein expression of C/EBPβ.

View Article: PubMed Central - PubMed

Affiliation: College of Life Sciences, Wuhan University, Wuhan 430072, PR China.

ABSTRACT
MicroRNA-191 (miR-191), a small non-coding RNA, is involved in disease development and cancer diagnosis and prognosis. However, how miR-191 functions in colorectal cancer remains largely unclear. In this study, we show that miR-191 is highly expressed in colon tumor tissues, and that inhibition of miR-191 leads to decreased cell growth, proliferation and tumorigenicity in a xenograft model. Overexpression of miR-191 in colorectal cancer cell lines alters cell cycle progression and cell resistance to 5-Fu induced cell apoptosis. Mechanistic studies demonstrated that miR-191 directly binds to the 3'UTR of the C/EBPβ mRNA and mediates a decrease in the mRNA and protein expression of C/EBPβ. We further showed that C/EBPβ induces growth arrest in a colorectal cancer cell line and that its expression is negatively correlated with the miR-191 level in patient samples. Our findings suggest that miR-191 may be a potential gene therapy target for the treatment of colorectal cancer.

No MeSH data available.


Related in: MedlinePlus

Schematic model of miR-191-mediated promotion of tumorigencity of colorectal cancer cellsIn colorectal cancer cells, various anticancer drugs regulate the expression of miR-191. miR-191 causes a number of genes to respond and adapt. On one hand, miR-191 induces the expression of CDK4 to increase cell growth. On the other hand, miR-191 suppresses the level of C/EBPβ, a tumor suppressor gene functions as a transcriptional activator of p15, p16 and p57, which are the key regulators of cell cycle and cell survival. As a result, miR-191 induces the cell cycle progression and tumor cell resistance to various stimuli.
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Figure 7: Schematic model of miR-191-mediated promotion of tumorigencity of colorectal cancer cellsIn colorectal cancer cells, various anticancer drugs regulate the expression of miR-191. miR-191 causes a number of genes to respond and adapt. On one hand, miR-191 induces the expression of CDK4 to increase cell growth. On the other hand, miR-191 suppresses the level of C/EBPβ, a tumor suppressor gene functions as a transcriptional activator of p15, p16 and p57, which are the key regulators of cell cycle and cell survival. As a result, miR-191 induces the cell cycle progression and tumor cell resistance to various stimuli.

Mentions: In the present report, we showed that up-regulation of miR-191 was a frequent event in colon cancers and that this up-regulation increased cell viability and promoted cell proliferation and tumorigenicity of HCT116 cells. Anticancer reagents, such as 5-Fu and etoposide, inhibited the expression of miR-191 and sustained up-regulation of miR1-191 reduced cell susceptibility to 5-Fu. C/EBPβ was identified as a target of miR-191 and ectopic expression of C/EBPβ impaired the effect of miR-191 overexpression on CRC by activating expression of downstream genes, including p15, p16 and p57 (Figure 7). Our results suggest a crucial role of miR-191 in tumorigenesis of CRC and provide a therapeutic approach for CRC treatment.


miR-191 promotes tumorigenesis of human colorectal cancer through targeting C/EBPβ.

Zhang XF, Li KK, Gao L, Li SZ, Chen K, Zhang JB, Wang D, Tu RF, Zhang JX, Tao KX, Wang G, Zhang XD - Oncotarget (2015)

Schematic model of miR-191-mediated promotion of tumorigencity of colorectal cancer cellsIn colorectal cancer cells, various anticancer drugs regulate the expression of miR-191. miR-191 causes a number of genes to respond and adapt. On one hand, miR-191 induces the expression of CDK4 to increase cell growth. On the other hand, miR-191 suppresses the level of C/EBPβ, a tumor suppressor gene functions as a transcriptional activator of p15, p16 and p57, which are the key regulators of cell cycle and cell survival. As a result, miR-191 induces the cell cycle progression and tumor cell resistance to various stimuli.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4414178&req=5

Figure 7: Schematic model of miR-191-mediated promotion of tumorigencity of colorectal cancer cellsIn colorectal cancer cells, various anticancer drugs regulate the expression of miR-191. miR-191 causes a number of genes to respond and adapt. On one hand, miR-191 induces the expression of CDK4 to increase cell growth. On the other hand, miR-191 suppresses the level of C/EBPβ, a tumor suppressor gene functions as a transcriptional activator of p15, p16 and p57, which are the key regulators of cell cycle and cell survival. As a result, miR-191 induces the cell cycle progression and tumor cell resistance to various stimuli.
Mentions: In the present report, we showed that up-regulation of miR-191 was a frequent event in colon cancers and that this up-regulation increased cell viability and promoted cell proliferation and tumorigenicity of HCT116 cells. Anticancer reagents, such as 5-Fu and etoposide, inhibited the expression of miR-191 and sustained up-regulation of miR1-191 reduced cell susceptibility to 5-Fu. C/EBPβ was identified as a target of miR-191 and ectopic expression of C/EBPβ impaired the effect of miR-191 overexpression on CRC by activating expression of downstream genes, including p15, p16 and p57 (Figure 7). Our results suggest a crucial role of miR-191 in tumorigenesis of CRC and provide a therapeutic approach for CRC treatment.

Bottom Line: In this study, we show that miR-191 is highly expressed in colon tumor tissues, and that inhibition of miR-191 leads to decreased cell growth, proliferation and tumorigenicity in a xenograft model.Overexpression of miR-191 in colorectal cancer cell lines alters cell cycle progression and cell resistance to 5-Fu induced cell apoptosis.Mechanistic studies demonstrated that miR-191 directly binds to the 3'UTR of the C/EBPβ mRNA and mediates a decrease in the mRNA and protein expression of C/EBPβ.

View Article: PubMed Central - PubMed

Affiliation: College of Life Sciences, Wuhan University, Wuhan 430072, PR China.

ABSTRACT
MicroRNA-191 (miR-191), a small non-coding RNA, is involved in disease development and cancer diagnosis and prognosis. However, how miR-191 functions in colorectal cancer remains largely unclear. In this study, we show that miR-191 is highly expressed in colon tumor tissues, and that inhibition of miR-191 leads to decreased cell growth, proliferation and tumorigenicity in a xenograft model. Overexpression of miR-191 in colorectal cancer cell lines alters cell cycle progression and cell resistance to 5-Fu induced cell apoptosis. Mechanistic studies demonstrated that miR-191 directly binds to the 3'UTR of the C/EBPβ mRNA and mediates a decrease in the mRNA and protein expression of C/EBPβ. We further showed that C/EBPβ induces growth arrest in a colorectal cancer cell line and that its expression is negatively correlated with the miR-191 level in patient samples. Our findings suggest that miR-191 may be a potential gene therapy target for the treatment of colorectal cancer.

No MeSH data available.


Related in: MedlinePlus