Downregulation of microRNA-124 is an independent prognostic factor in patients with colorectal cancer

Wang, Mo-Jin; Li, Yuan; Wang, Rui; Wang, Cun; Yu, Yanyan; Yang, Lie; Zhang, Yi; Zhou, Bin; Zhou, Zong‐Guang; Sun, Xiao‐Feng

doi:10.1007/s00384-012-1550-3

Cited by 58 publications

(40 citation statements)

References 30 publications

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“…Its mature sequence is processed from three precursor variants that are located at chromosomes 8p23.1 (miR-124-1), 8q12.3 (miR-124-2) and 20q13.33 (miR-124-3), respectively. Studies have shown that miR-124 is down-expressed in various types of cancer, which is inversely associated with tumor growth, lymph node metastasis, and poor prognosis [18–22]. However, there are studies that show different expression patterns and functions of miR-124 in cancer.…”

Section: Introductionmentioning

confidence: 99%

MiR-124 acts as a tumor suppressor by inhibiting the expression of sphingosine kinase 1 and its downstream signaling in head and neck squamous cell carcinoma

et al. 2017

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By analyzing the expression profile of microRNAs in head and neck squamous cell carcinomas (HNSCC), we found that the expression level of miR-124 was 4.59-fold lower in tumors than in normal tissues. To understand its functions, we generated a miR-124-expressing subline (JHU-22miR124) and a mock vector-transfected subline (JHU-22vec) by transfecting the mimic of miR-124 into JHU-22 cancer cells. Restored expression of miR-124 in JHU-22miR124 cells led to reduced cell proliferation, delayed colony formation, and decreased tumor growth, indicating a tumor-suppressive effect of miR-124. Subsequent target search revealed that the 3′-UTR of SphK1 mRNA carries a complementary site for the seed region of miR-124. SphK1 was also detected to be overexpressed in HNSCC cell lines, but down-expressed in JHU-22miR124 cells and tumor xenografts. These results suggest that SphK1 is a target of miR-124. To confirm this finding, we constructed a 3′-UTR-Luc-SphK1 vector and a binding site-mutated luciferase reporter vector. Co-transfection of 3′-UTR-Luc-SphK1 with miR-124 expression vector exhibited a 9-fold decrease in luciferase activity compared with mutated vector, suggesting that miR-124 inhibits SphK1 activity directly. Further studies on downstream signaling demonstrated accumulation of ceramide, increased expression of the pro-apoptotic Bax, BAD and PARP, decreased expression of the anti-apoptotic Bcl-2 and Bcl-xL, and enhanced expression of cytochrome c and caspase proteins in JHU-22miR124 compared with JHU-22vec cells and tumor xenografts. We conclude that miR-124 acts as a tumor suppressor in HNSCC by directly inhibiting SphK1 activity and its downstream signals.

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Section: Introductionmentioning

confidence: 99%

MiR-124 acts as a tumor suppressor by inhibiting the expression of sphingosine kinase 1 and its downstream signaling in head and neck squamous cell carcinoma

et al. 2017

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“…Thereafter, investigation of miRNAs would be useful to expand our insight to better understand colorectal carcinogenesis as a potential tumor oncogene by analyzing associated mRNA targets and miRNA-mediated pathways. 21,22 There are many reports on the effects of miRNAs on oncogenes and tumor suppressor genes. 23 One study showed that down regulation of miR-383 was correlated with enhanced proliferative activity of germ cells in maturation arrest patients.…”

Section: Capability Of Mir-383 To Function As a Colorectal Cancer Tummentioning

confidence: 99%

“…5 Therefore, knowing more about the biology and nature of colorectal cancer, it is possible to design effective prognostic, diagnostic, and treatment plans to help reduce the rate of this disease. 6 MicroRNAs (miRNAs) are a class of small (18)(19)(20)(21)(22)(23)(24) noncoding RNAs that regulate gene expression at post translation levels. 7,8 This molecular RNAs regulate many biological processes.…”

Section: Introductionmentioning

confidence: 99%

Prognostic and predictive roles of microRNA-383 in colorectal cancer

Fateh

Feizi

Safaralizadeh

et al. 2016

Gastroenterol Insights

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MicroRNAs (miRNAs) are impressive regulators of gene expression that have a critical role in the pathogenesis of colorectal cancer (CRC). With respect to the aberrant expression of miRNA-383 (miR-383) in some types of human malignancy, this prospective study characterized its contribution to CRC tumorigenesis. The real-time reverse transcriptionpolymerase chain reaction was used to examine miR-383 expression levels prospectively in 40 sample pairs of CRC tissues and adjacent noncancerous tissues (>2 cm from cancer tissue). No significant relationship was found between miR-383 expression levels and clinicopathological features. The ability of miR-383 to function as a tumor marker was also examined. Showing significant changes overall, miR-383 expression levels were significantly down regulated in the group of CRC samples compared with matched noncancerous tissue samples. A receiver-operating characteristic (ROC) curve also showed ROC area of 70% for miR-383 with 68 and 75% sensitivity and specificity, respectively. Therefore, miR-383 can be considered as a tumor marker in CRC and help as a potential predictive biomarker in the diagnosis of colorectal cancer.

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“…Moreover, downregulated miR-124 expression was previously identified in patients with breast cancer, 25 clear-cell renal cell carcinoma, 26 cervical cancer, 27 and colorectal cancer, 28 and these studies show that decreased miR-124 expression closely correlated with poor clinical outcomes. Consistent with these reports, our clinical data also show that the expression of miR-124 level negatively correlated with the overall survival of NSCLC patients, and our multivariate analysis indicates that miR-124 may be a useful independent biomarker for predicting NSCLC disease progression.…”

Section: Discussionmentioning

confidence: 63%

miR-124 Inhibits Lung Tumorigenesis Induced by K-ras Mutation and NNK

Jin

Cao

et al. 2017

Molecular Therapy - Nucleic Acids

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Dysregulated miRNAs play important role in K-ras mutation or smoking caused lung tumorigenesis. Here, we investigate the role and mechanism of miR-124 in K-ras mutation or smoking-caused lung tumorigenesis and evaluate the therapeutic potential of miR-124 agomiR in K-ras mutation or smoking-caused lung cancer treatment. Our data show that smoking suppresses miR-124 expression, and decreased miR-124 expression is inversely correlated with the p-Akt level and predicts poor overall survival in non-small-cell lung cancer (NSCLC) patients. The overexpression of miR-124 suppressed NSCLC growth by inhibiting the Akt pathway by targeting Akt1 and Akt2. In addition, the systemic delivery of miR-124 agomiR dramatically suppressed tumorigenesis in both NNK-induced lung cancer model and K-rasLA1 transgenic mice by increasing apoptosis and inhibiting cell proliferation. Our findings suggest that smoking inhibits the expression of miR-124, and decreased miR-124 contributes to Akt activation, thereby promoting NSCLC progression. Our findings also represent a novel potential therapeutic strategy for lung cancer.

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Downregulation of microRNA-124 is an independent prognostic factor in patients with colorectal cancer

Cited by 58 publications

References 30 publications

MiR-124 acts as a tumor suppressor by inhibiting the expression of sphingosine kinase 1 and its downstream signaling in head and neck squamous cell carcinoma

MiR-124 acts as a tumor suppressor by inhibiting the expression of sphingosine kinase 1 and its downstream signaling in head and neck squamous cell carcinoma

Prognostic and predictive roles of microRNA-383 in colorectal cancer

miR-124 Inhibits Lung Tumorigenesis Induced by K-ras Mutation and NNK

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