Restoration of tumor suppressor miR-34 inhibits human p53-mutant gastric cancer tumorspheres

Ji, Qing; Hao, Xinbao; Meng, Yan; Zhang, Min; DeSano, Jeffrey; Fan, Daiming; Xu, Liang

doi:10.1186/1471-2407-8-266

Cited by 358 publications

(288 citation statements)

References 51 publications

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“…Both forms of the lymphomas have definitive clinicopathological entities characterized by their unique histological and clinical features [1][2][3]. Research showed that miR-34a regulation of B-cell development and apoptosis were possibly related to the tumor suppressor p53, oncogenic protein BCL2, and FOXP1 [10][11][12][13][14][15][16][17][18]. In this study, we assessed corelations of miR-34a level and the expression of the B-cell differentiation-and apoptosisrelated proteins FOXP1, p53, and BCL2 with the clinicopathological features and survival of gastric MALT lymphoma and DLBCL.…”

Section: Follow-up and Survivalmentioning

confidence: 99%

“…The same studies showed that BCL2 was targeted by miR-34a, and that there was a direct interaction between miR-34a and the tumor suppressor p53 and the oncogenic protein BCL2. This interaction was shown to increase the survival of miR-34a-expressing pro-B cells but did not significantly promote their differentiation [10,11,13,14]. Other studies have shown that the forkhead box protein 1 (FOXP1) is involved in B-cell differentiation and survival [15].…”

mentioning

confidence: 99%

“…It has also been shown that miR-34a-induced apoptosis is at least partly dependent on the presence of wild-type p53 genes, indicating that miR34a may feed back to p53 [8][9][10][11]. In similar studies, the status of p53 deletion or mutation was associated with miR-34a downregulation in prostate cancer, gastric cancer, and chronic B-cell lymphocytic leukemia [11,12]. The same studies showed that BCL2 was targeted by miR-34a, and that there was a direct interaction between miR-34a and the tumor suppressor p53 and the oncogenic protein BCL2.…”

mentioning

confidence: 99%

“…In the past few years, some studies suggest that miR-NA-34a may act as a tumor suppressor by regulating apoptosis in several tumors [7]. It has also been shown that miR-34a-induced apoptosis is at least partly dependent on the presence of wild-type p53 genes, indicating that miR34a may feed back to p53 [8][9][10][11]. In similar studies, the status of p53 deletion or mutation was associated with miR-34a downregulation in prostate cancer, gastric cancer, and chronic B-cell lymphocytic leukemia [11,12].…”

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confidence: 99%

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Prognostic significance of miR-34a and its target proteins of FOXP1, p53, and BCL2 in gastric MALT lymphoma and DLBCL

He¹,

Li²,

Zhang³

et al. 2013

Gastric Cancer

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Background Mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma (DLBCL), which are the two most common types of gastric lymphomas, have different clinicopathological features and molecular characteristics with distinct clinical outcomes. Tumor suppressor miR-34a connects the p53 network with forkhead box protein 1 (FOXP1) and BCL2. Here, we investigated the prognostic value of these molecules in gastric MALT lymphoma and DLBCL for use in routine clinical practice. Methods Relative miR-34a expression was detected by quantitative reverse transcriptase-polymerase chain reaction in 20 cases of MALT lymphomas and 20 cases of DLBCLs. Tissue microarray, in situ hybridization, and immunohistochemistry analysis were used to examine the expression of miR-34a and its regulated genes, FOXP1, p53, and BCL2 proteins, in 64 patients with gastric MALT lymphoma and in 58 patients with DLBCL. Helicobacter pylori infection, overall survival (OS), and progression-free survival (PFS) were documented. Results The expression level of miR-34a was markedly decreased in MALT lymphomas and DLBCLs compared to normal gastric tissues and peripheral blood mononuclear cells. miR-34a was present in the cytoplasm and nucleus of lymphocytes. Its expression was significantly downregulated in MALT and DLBCL lymphoma tissues, as compared with normal lymphocytes. The expression level of miR-34a in DLBCL was lower than in MALT lymphoma. FOXP1 was found to be positive in 48 %, p53 in 20 %, and BCL2 in 68 % of MALT lymphoma cases. The corresponding positive rates of these markers in DLBCL were 64, 57, and 52 %, respectively. High expression of FOXP1, p53, and BCL2 was seen in stage III and IV of both types of lymphomas. FOXP1, p53, and BCL2 positivity was associated with poor OS with both lymphoma types but OS with DLBCL was significantly lower than with MALT lymphoma. Conclusions Decreased miR-34a expression and increased FOXP1, p53, and BCL2 coexpression to predict a poor OS for MALT lymphoma and DLBCL patients could become very important prognostic markers in daily clinical work. Further investigation of these changes may be of prognostic significance in clinical practice.

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Section: Follow-up and Survivalmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Prognostic significance of miR-34a and its target proteins of FOXP1, p53, and BCL2 in gastric MALT lymphoma and DLBCL

He¹,

Li²,

Zhang³

et al. 2013

Gastric Cancer

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“…When introduced into cancer cells, miR34a induces cell-cycle arrest (6), senescence (7), and apoptosis (7). The miRNA also inhibits cancer stem cell development (8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Systemic Delivery of a miR34a Mimic as a Potential Therapeutic for Liver Cancer

Daige

Wiggins

Priddy

et al. 2014

Molecular Cancer Therapeutics

149

103

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miR34a is a tumor-suppressor miRNA that functions within the p53 pathway to regulate cell-cycle progression and apoptosis. With apparent roles in metastasis and cancer stem cell development, miR34a provides an interesting opportunity for therapeutic development. A mimic of miR34a was complexed with an amphoteric liposomal formulation and tested in two different orthotopic models of liver cancer. Systemic dosing of the formulated miR34a mimic increased the levels of miR34a in tumors by approximately 1,000-fold and caused statistically significant decreases in the mRNA levels of several miR34a targets. The administration of the formulated miR34a mimic caused significant tumor growth inhibition in both models of liver cancer, and tumor regression was observed in more than one third of the animals. The antitumor activity was observed in the absence of any immunostimulatory effects or dose-limiting toxicities. Accumulation of the formulated miR34a mimic was also noted in the spleen, lung, and kidney, suggesting the potential for therapeutic use in other cancers. Mol Cancer Ther; 13(10); 2352-60. Ó2014 AACR.

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MicroRNA Regulation of Cancer Stem Cells and MicroRNAs as Potential Cancer Stem Cell Therapeutics

Liu

Tang

2013

MicroRNAs in Medicine

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Restoration of tumor suppressor miR-34 inhibits human p53-mutant gastric cancer tumorspheres

Cited by 358 publications

References 51 publications

Prognostic significance of miR-34a and its target proteins of FOXP1, p53, and BCL2 in gastric MALT lymphoma and DLBCL

Prognostic significance of miR-34a and its target proteins of FOXP1, p53, and BCL2 in gastric MALT lymphoma and DLBCL

Systemic Delivery of a miR34a Mimic as a Potential Therapeutic for Liver Cancer

MicroRNA Regulation of Cancer Stem Cells and MicroRNAs as Potential Cancer Stem Cell Therapeutics

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