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MicroRNA-218 inhibits the proliferation and metastasis of esophageal squamous cell carcinoma cells by targeting BMI1.

Wang T, Chen T, Niu H, Li C, Xu C, Li Y, Huang R, Zhao J, Wu S - Int. J. Mol. Med. (2015)

Bottom Line: MicroRNAs (miRNAs or miRs) play a pivotal role in esophageal carcinogenesis either as oncogenes or as tumor suppressor genes.Furthermore, the decreased expression of miR-218 was found to be associated with an enhanced ESCC cell proliferation and metastasis.In the present study, our findings confirm miR-218 as a tumor suppressor and identify BMI1 as a novel target of miR-218 in ESCC.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Medical College of Soochow University, Suzhou, Jiangsu 215123, P.R. China.

ABSTRACT
MicroRNAs (miRNAs or miRs) play a pivotal role in esophageal carcinogenesis either as oncogenes or as tumor suppressor genes. In the present study, we found that the expression level of miR-218 was significantly reduced in esophageal squamous cell carcinoma (ESCC) tissues and ESCC cell lines. Moreover, its expression was found to correlate with the clinicopathological stage of ESCC; miR-218 expression was lower in the stage III tissue samples than in the stage I and II tissue samples. Furthermore, the decreased expression of miR-218 was found to be associated with an enhanced ESCC cell proliferation and metastasis. Western blot analysis and luciferase reporter assay revealed that miR-218 decreased BMI1 expression by binding to the putative binding sites in its 3'-untranslated region (3'-UTR). The BMI1 mRNA expression levels were markedly increased and negatively correlated with the miR-218 expression level in the ESCC tissues. Functional analyses revealed that the restoration of miR-218 expression inhibited ESCC cell proliferation, migration and invasion and promoted apoptosis. The knockdown of BMI1 by siRNA showed the same phenocopy as the effect of miR-218 on ESCC cells, indicating that BMI1 was a major target of miR-218. In the present study, our findings confirm miR-218 as a tumor suppressor and identify BMI1 as a novel target of miR-218 in ESCC. Therefore, miR-218 may prove to be a useful biomarker for monitoring the initiation and development of ESCC, and may thus be an effective therapeutic target in ESCC.

No MeSH data available.


Related in: MedlinePlus

The decreased expression of miR-218 in esophageal squamous cell carcinoma (ESCC) tissues and ESCC cell lines. (A) Expression of miR-218 in 33 ESCC tissue samples and paired adjacent normal tissue samples detected by RT-qPCR. (B) Expression of miR-218 in human esophageal epithelial cells (HEECs) and 4 ESCC cell lines quantified by RT-qPCR. Data are presented as the means ± SD from 3 replicate samples. **P<0.01, ***P<0.001.
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f1-ijmm-36-01-0093: The decreased expression of miR-218 in esophageal squamous cell carcinoma (ESCC) tissues and ESCC cell lines. (A) Expression of miR-218 in 33 ESCC tissue samples and paired adjacent normal tissue samples detected by RT-qPCR. (B) Expression of miR-218 in human esophageal epithelial cells (HEECs) and 4 ESCC cell lines quantified by RT-qPCR. Data are presented as the means ± SD from 3 replicate samples. **P<0.01, ***P<0.001.

Mentions: In order to determine the role of miR-218 in ESCC, the miR-218 expression levels were determined in tissue samples from 33 patient with ESCC and their paired adjacent normal tissue samples. As shown in Fig. 1A, miR-218 expression was significantly decreased in the ESCC tissues when compared with the paired normal tissues. More importantly, the decreased expression of miR-218 was also associated with the clinicopathological stages of ESCC; the miR-218 expression levels were downregulated to a greater extent in the tissue samples from patients with stage III ESCC than those from patients with stageI and II ESCC (Table II). In addition, the decreased miR-218 expression correlated with the ESCC differentiation stage.


MicroRNA-218 inhibits the proliferation and metastasis of esophageal squamous cell carcinoma cells by targeting BMI1.

Wang T, Chen T, Niu H, Li C, Xu C, Li Y, Huang R, Zhao J, Wu S - Int. J. Mol. Med. (2015)

The decreased expression of miR-218 in esophageal squamous cell carcinoma (ESCC) tissues and ESCC cell lines. (A) Expression of miR-218 in 33 ESCC tissue samples and paired adjacent normal tissue samples detected by RT-qPCR. (B) Expression of miR-218 in human esophageal epithelial cells (HEECs) and 4 ESCC cell lines quantified by RT-qPCR. Data are presented as the means ± SD from 3 replicate samples. **P<0.01, ***P<0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494586&req=5

f1-ijmm-36-01-0093: The decreased expression of miR-218 in esophageal squamous cell carcinoma (ESCC) tissues and ESCC cell lines. (A) Expression of miR-218 in 33 ESCC tissue samples and paired adjacent normal tissue samples detected by RT-qPCR. (B) Expression of miR-218 in human esophageal epithelial cells (HEECs) and 4 ESCC cell lines quantified by RT-qPCR. Data are presented as the means ± SD from 3 replicate samples. **P<0.01, ***P<0.001.
Mentions: In order to determine the role of miR-218 in ESCC, the miR-218 expression levels were determined in tissue samples from 33 patient with ESCC and their paired adjacent normal tissue samples. As shown in Fig. 1A, miR-218 expression was significantly decreased in the ESCC tissues when compared with the paired normal tissues. More importantly, the decreased expression of miR-218 was also associated with the clinicopathological stages of ESCC; the miR-218 expression levels were downregulated to a greater extent in the tissue samples from patients with stage III ESCC than those from patients with stageI and II ESCC (Table II). In addition, the decreased miR-218 expression correlated with the ESCC differentiation stage.

Bottom Line: MicroRNAs (miRNAs or miRs) play a pivotal role in esophageal carcinogenesis either as oncogenes or as tumor suppressor genes.Furthermore, the decreased expression of miR-218 was found to be associated with an enhanced ESCC cell proliferation and metastasis.In the present study, our findings confirm miR-218 as a tumor suppressor and identify BMI1 as a novel target of miR-218 in ESCC.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Medical College of Soochow University, Suzhou, Jiangsu 215123, P.R. China.

ABSTRACT
MicroRNAs (miRNAs or miRs) play a pivotal role in esophageal carcinogenesis either as oncogenes or as tumor suppressor genes. In the present study, we found that the expression level of miR-218 was significantly reduced in esophageal squamous cell carcinoma (ESCC) tissues and ESCC cell lines. Moreover, its expression was found to correlate with the clinicopathological stage of ESCC; miR-218 expression was lower in the stage III tissue samples than in the stage I and II tissue samples. Furthermore, the decreased expression of miR-218 was found to be associated with an enhanced ESCC cell proliferation and metastasis. Western blot analysis and luciferase reporter assay revealed that miR-218 decreased BMI1 expression by binding to the putative binding sites in its 3'-untranslated region (3'-UTR). The BMI1 mRNA expression levels were markedly increased and negatively correlated with the miR-218 expression level in the ESCC tissues. Functional analyses revealed that the restoration of miR-218 expression inhibited ESCC cell proliferation, migration and invasion and promoted apoptosis. The knockdown of BMI1 by siRNA showed the same phenocopy as the effect of miR-218 on ESCC cells, indicating that BMI1 was a major target of miR-218. In the present study, our findings confirm miR-218 as a tumor suppressor and identify BMI1 as a novel target of miR-218 in ESCC. Therefore, miR-218 may prove to be a useful biomarker for monitoring the initiation and development of ESCC, and may thus be an effective therapeutic target in ESCC.

No MeSH data available.


Related in: MedlinePlus