A Short Hairpin DNA Analogous to miR-125b Inhibits C-Raf Expression, Proliferation, and Survival of Breast Cancer Cells

Hofmann, Marco H.; Heinrich, Joachim; Radziwil, Gerald; Moelling, Karin

doi:10.1158/1541-7786.mcr-09-0043

Cited by 53 publications

(29 citation statements)

References 64 publications

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“…Raf-1 has been found to be overexpressed or overactivated in a variety of cancers, including renal cell carcinoma, hepatocellular carcinoma, non-small cell lung cancer, melanoma, and papillary thyroid carcinoma (32). Recently, Raf-1 was found to be a target of miR-7 and miR-125b (33,34). In breast cancer, miR-125b could target the same region of c-Raf-1 (34).…”

Section: Discussionmentioning

confidence: 99%

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Analysis of MiR-195 and MiR-497 Expression, Regulation and Role in Breast Cancer

Zhao

Liu

et al. 2011

Clinical Cancer Research

286

257

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Purpose: To investigate expression, regulation, potential role and targets of miR-195 and miR-497 in breast cancer.Experimental Design: The expression patterns of miR-195 and miR-497 were initially examined in breast cancer tissues and cell lines by Northern blotting and quantitative real-time PCR. Combined bisulfite restriction analysis and bisulfite sequencing were carried out to study the DNA methylation status of miR-195 and miR-497 genes. Breast cancer cells stably expressing miR-195 and miR-497 were established to study their role and targets. Finally, normal, fibroadenoma and breast cancer tissues were employed to analyze the correlation between miR-195/497 levels and malignant stages of breast tumor tissues.Results: MiR-195 and miR-497 were significantly downregulated in breast cancer. The methylation state of CpG islands upstream of the miR-195/497 gene was found to be responsible for the downregulation of both miRNAs. Forced expression of miR-195 or miR-497 suppressed breast cancer cell proliferation and invasion. Raf-1 and Ccnd1 were identified as novel direct targets of miR-195 and miR-497. miR-195/497 expression levels in clinical specimens were found to be correlated inversely with malignancy of breast cancer.Conclusions: Our data imply that both miR-195 and miR-497 play important inhibitory roles in breast cancer malignancy and may be the potential therapeutic and diagnostic targets.

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Section: Discussionmentioning

confidence: 99%

“…Recently, Raf-1 was found to be a target of miR-7 and miR-125b (33,34). In breast cancer, miR-125b could target the same region of c-Raf-1 (34). In addition, Raf-1 was identified as a direct target of miR-7 in several cancer cell lines, including breast cancer (33).…”

Section: Discussionmentioning

confidence: 99%

Analysis of MiR-195 and MiR-497 Expression, Regulation and Role in Breast Cancer

Zhao

Liu

et al. 2011

Clinical Cancer Research

286

257

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“…Overexpression of miR-125b promotes the proliferation of glial cells 7 but suppresses the proliferation of ovarian, bladder, breast and liver cancer cells. 6,[11][12][13] Regulators of proliferation, including BCL3, CDKN2A, E2F3, RAF1, ETS1, LIN28B2, ERBB3, ERBB2 and placenta growth factor 6,7,[11][12][13][14][15][16] have been identified as direct targets of miR-125b. It has been shown that overexpression of miR-125b inhibits apoptosis in glioma and prostate cancer cells, and miR-125b regulates the expression of pro-apoptotic proteins such as p53, Bak1, Puma and Bmf.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-125b promotes apoptosis by regulating the expression of Mcl-1, Bcl-w and IL-6R

Gong

Li³

et al. 2012

Oncogene

181

135

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The microRNA miR-125b is multi-faceted, with the ability to function as a tumor suppressor or an oncogene, depending on the cellular context. To date, the pro-apoptotic role of miR-125b and its underlying mechanisms are unexplored. In this study, both gain- and loss-of-function experiments revealed that miR-125b expression not only induced spontaneous apoptosis in various cell lines derived from the liver, lung and colorectal cancers, but also sensitized cancer cells to diverse apoptotic stimuli, including nutrient starvation and chemotherapeutic treatment. Furthermore, downregulation of miR-125b was a frequent event in hepatocellular carcinoma (HCC) tissues, and the miR-125b level was positively associated with the rate of apoptosis in HCC tissues. Subsequent investigations identified Mcl-1, Bcl-w and interleukin (IL)-6R as direct targets of miR-125b. Restoration of miR-125b expression not only diminished the expression of Mcl-1 and Bcl-w directly but also indirectly reduced the Mcl-1 and Bcl-xL levels by attenuating IL-6/signal transducer and activator of transcription 3 signaling. Consistent with these findings, introduction of miR-125b reduced the mitochondrial membrane potential and promoted the cleavage of pro-caspase-3. These data indicate that miR-125b may promote apoptosis by suppressing the anti-apoptotic molecules of the Bcl-2 family and miR-125b downregulation may facilitate tumor development by conferring upon cells the capability to survive under conditions of nutrient deprivation and chemotherapeutic treatment. Our findings highlight the importance of miR-125b in the regulation of apoptosis and suggest miR-125b as an attractive target for anti-cancer therapy.

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“…Another confirmed target of miR-125 family is MUC I (Mucin I) oncogene in breast cancer (Rajabi et al, 2010). In addition, a short hairpin DNA analogous to miR-125b was used to target C-Raf expression and this negatively affected the proliferation and survival of breast cancer cells (Hofmann et al, 2009). miR-125b was also reported to have negative effects on cellular proliferation of breast cancer cells in an ERBB2 dependent manner (Scott et al, 2007).…”

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confidence: 99%

miR-125b Targets ARID3B in Breast Cancer Cells

Akhavantabasi¹,

Sapmaz²,

Tuna³

et al. 2012

Cell Struct. Funct.

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ABSTRACT. Mounting evidence suggests involvement of deregulated microRNA (miRNA) expression during the complex events of tumorigenesis. Among such deregulated miRNAs in cancer, miR-125b expression is reported to be consistently low in breast cancers. In this study, we screened a panel of breast cancer cell lines (BCCLs) for miR-125b expression and detected decreased expression in 14 of 19 BCCLs. Due to the heterogeneity of breast cancers, MCF7 cells were chosen as a model system for ERBB2 independent breast cancers to restore miR-125b expression (MCF7-125b) to investigate the phenotypical and related functional changes. Earlier, miR-125b was shown to regulate cell motility by targeting ERBB2 in ERBB2 overexpressing breast cancer cells. Here we showed decreased motility and migration in miR-125b expressing MCF7 cells, independent of ERBB2. MCF7-125b cells demonstrated profoundly decreased cytoplasmic protrusions detected by phalloidin staining of filamentous actin along with decreased motility and migration behaviors detected by in vitro wound closure and transwell migration assays compared to empty vector transfected cells (MCF7-EV). Among possible numerous targets of miR-125b, we showed ARID3B (AT-rich interactive domain 3B) to be a novel target with roles in cell motility in breast cancer cells. When ARID3B was transiently silenced, the decreased cell migration was also observed. In light of these findings, miR-125b continues to emerge as an interesting regulator of cancer related phenotypes.

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A Short Hairpin DNA Analogous to miR-125b Inhibits C-Raf Expression, Proliferation, and Survival of Breast Cancer Cells

Cited by 53 publications

References 64 publications

Analysis of MiR-195 and MiR-497 Expression, Regulation and Role in Breast Cancer

Analysis of MiR-195 and MiR-497 Expression, Regulation and Role in Breast Cancer

MicroRNA-125b promotes apoptosis by regulating the expression of Mcl-1, Bcl-w and IL-6R

miR-125b Targets ARID3B in Breast Cancer Cells

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