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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

miR-191 is up-regulated in colon cancersStem-loop RT-PCR analysis of the miR-191 level in tissues and cell lines. (A) Relative miR-191 expression in 16 paired colon cancer tissues and adjacent non-tumor tissues (upper panel). miR-191 expression values were expressed as ratios with U6 snRNA (×10). (lower panel, P = 0.011) The statistical significance was evaluated by paired-samples T test. (B) Relative miR-191 expression in five human colorectal cancer cell lines (HCT116, RKO, HT29, SW480, DLD1 and Lovo) and human embryonic kidney 293T cells. U6 snRNA was used as an internal control. The data represents the means ± SDs.
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Figure 1: miR-191 is up-regulated in colon cancersStem-loop RT-PCR analysis of the miR-191 level in tissues and cell lines. (A) Relative miR-191 expression in 16 paired colon cancer tissues and adjacent non-tumor tissues (upper panel). miR-191 expression values were expressed as ratios with U6 snRNA (×10). (lower panel, P = 0.011) The statistical significance was evaluated by paired-samples T test. (B) Relative miR-191 expression in five human colorectal cancer cell lines (HCT116, RKO, HT29, SW480, DLD1 and Lovo) and human embryonic kidney 293T cells. U6 snRNA was used as an internal control. The data represents the means ± SDs.

Mentions: Several reports indicated that miR-191 is up-regulated in human colorectal cancers by using high throughput sequencing [22–24]. Here, miR-191 expression was further analyzed in 16 paired colon and adjacent non-tumor colon tissues by way of real-time PCR. Our results demonstrated that miR-191 was up-regulated in the majority of examined tumor tissues, with 10 of 16 (62.5%) tumor tissues displaying a more than 38% increase, which suggested a probable ‘oncomiR’ role of miR-191 in colorectal cancer. Notably, there were three colon cancer tissues displayed a 3-fold down-regulation of miR-191 expression. (Figure 1A) We next examined miR-191 expression in five human colorectal cancer cell lines (HCT116, RKO, HT29, SW480, DLD1 and Lovo) and HEK293T cells by quantitative PCR. miR-191 was expressed in all six cell lines, and HCT116 displayed a higher expression level of miR-191 (Figure 1B). So, we used HCT116 cells as a model to investigate the effect of miR191 on cell growth and proliferation.


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)

miR-191 is up-regulated in colon cancersStem-loop RT-PCR analysis of the miR-191 level in tissues and cell lines. (A) Relative miR-191 expression in 16 paired colon cancer tissues and adjacent non-tumor tissues (upper panel). miR-191 expression values were expressed as ratios with U6 snRNA (×10). (lower panel, P = 0.011) The statistical significance was evaluated by paired-samples T test. (B) Relative miR-191 expression in five human colorectal cancer cell lines (HCT116, RKO, HT29, SW480, DLD1 and Lovo) and human embryonic kidney 293T cells. U6 snRNA was used as an internal control. The data represents the means ± SDs.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: miR-191 is up-regulated in colon cancersStem-loop RT-PCR analysis of the miR-191 level in tissues and cell lines. (A) Relative miR-191 expression in 16 paired colon cancer tissues and adjacent non-tumor tissues (upper panel). miR-191 expression values were expressed as ratios with U6 snRNA (×10). (lower panel, P = 0.011) The statistical significance was evaluated by paired-samples T test. (B) Relative miR-191 expression in five human colorectal cancer cell lines (HCT116, RKO, HT29, SW480, DLD1 and Lovo) and human embryonic kidney 293T cells. U6 snRNA was used as an internal control. The data represents the means ± SDs.
Mentions: Several reports indicated that miR-191 is up-regulated in human colorectal cancers by using high throughput sequencing [22–24]. Here, miR-191 expression was further analyzed in 16 paired colon and adjacent non-tumor colon tissues by way of real-time PCR. Our results demonstrated that miR-191 was up-regulated in the majority of examined tumor tissues, with 10 of 16 (62.5%) tumor tissues displaying a more than 38% increase, which suggested a probable ‘oncomiR’ role of miR-191 in colorectal cancer. Notably, there were three colon cancer tissues displayed a 3-fold down-regulation of miR-191 expression. (Figure 1A) We next examined miR-191 expression in five human colorectal cancer cell lines (HCT116, RKO, HT29, SW480, DLD1 and Lovo) and HEK293T cells by quantitative PCR. miR-191 was expressed in all six cell lines, and HCT116 displayed a higher expression level of miR-191 (Figure 1B). So, we used HCT116 cells as a model to investigate the effect of miR191 on cell growth and proliferation.

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