RETRACTED ARTICLE: Down-regulated microRNA-124 expression as predictive biomarker and its prognostic significance with clinicopathological features in breast cancer patients

Arabkheradmand, Ali; Safari, Aghdas; Seifoleslami, Mehri; Yahaghi, Emad; Gity, Masoumeh

doi:10.1186/s13000-015-0391-0

Cited by 10 publications

(9 citation statements)

References 23 publications

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“…Second, we only focused on HER-2 positive breast cancer, so further studies are required to validate the association between miR-124 expression, HER2 status, and radioresistance in different cancer subtypes. Interestingly, Arabkheradmand et al (11) reported an association between miR-124 down-regulation and advanced clinical stage and the presence of lymph node metastasis in Iranian patients with breast cancer, however, they found no association between microRNA expression and HER2 status. There are several explanations for the difference between our study and the study by Arabkheradmand et al: 1) The complex relation between miRNA expression and clinic clinicopathological characteristics of the patients might be different in the Iranian and Chinese Han populations.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-124 enhances response to radiotherapy in human epidermal growth factor receptor 2-positive breast cancer cells by targeting signal transducer and activator of transcription 3

Xiong

2016

Croat Med J

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AimTo determine whether microRNA (miR)-124 enhances the response to radiotherapy in human epidermal growth factor receptor 2 (HER2)-positive breast cancer cells by targeting signal transducer and activator of transcription 3 (Stat3).MethodsmiR-29b expression was measured in 80 pairs of breast tumor samples and adjacent normal tissues collected between January 2013 and July 2014. Activity changes of 50 canonical signaling pathways upon miR-124 overexpression were determined using Cignal Signal Transduction Reporter Array. Target gene of miR-124 was determined using Targetscan and validated by Western blotting and dual-luciferase assay. Cell death rate was assessed by propidium iodide (PI)/ Annexin V staining followed by flow cytometry analysis. Stat3 and miR-124 expression was further measured in 10 relapsed (non-responder) and 10 recurrence-free HER2-positive breast cancer patients.ResultsMiR-124 expression was down-regulated in HER2 positive breast cancers compared with normal tissues, and was negatively associated with tumor size. MiR-124 overexpression in HER2 positive breast cancer cell line SKBR3 significantly reduced the activity of Stat3 signaling pathway compared with control transfection (P < 0.001). Bioinformatic prediction and function assay suggested that miR-124 directly targeted Stat3, which is a key regulator of HER2 expression. MiR-124 overexpression down-regulated Stat3 and potently enhanced cell death upon irradiation. Consistently, chemical inhibitor of Stat3 also sensitized HER2-positive breast cancer cells to irradiation. Moreover, increased Stat3 expression and reduced miR-124 expression were associated with a poor response to radiotherapy in HER2-positive breast cancers.ConclusionsWeak miR-124 expression might enhance Stat3 expression and radiotherapy resistance in HER2-positive breast cancer cells.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-124 enhances response to radiotherapy in human epidermal growth factor receptor 2-positive breast cancer cells by targeting signal transducer and activator of transcription 3

Xiong

2016

Croat Med J

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“…In HNSCC, the epithelial-restricted with serine box/epidermal growth factor receptor (EGFR) and ITGB1 have been reported to be the targets of miR-124 [21, 33]. By a comprehensive search, we found that the 3′-UTR sequence of SphK1 mRNA carries a complementary site for the seed region of miR-124.…”

Section: Discussionmentioning

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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“…As a tumor suppressor, aberrant low expression of miR-124 is often detected in many tumors, such as gynecological, cerebral, and gastric tumors454647. MiR-124 was reported to perform crucial anti-cancer functions in GC4849.…”

Section: Discussionmentioning

confidence: 99%

Sulforaphane improves chemotherapy efficacy by targeting cancer stem cell-like properties via the miR-124/IL-6R/STAT3 axis

Wang

Dai

et al. 2016

Sci Rep

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Gastric carcinoma (GC) is the second leading cause of cancer-related mortality worldwide. The efficacy of standard chemotherapy for GC, such as cisplatin (CDDP), is dissatisfactory partly due to the toxic/side-effects. Sulforaphane (SFN), which exhibits effective anti-cancer functions, is a phytochemical converted from cruciferous plants. Our present study aimed to identify whether SFN could enhance the anti-cancer effects of low-dose CDDP and to determine the underlying mechanisms. Herein, co-exposure of SFN and CDDP significantly inhibited the viabilities of gastric cancer cells. For the molecular mechanisms, CDDP alone increased the cancer stem cell (CSC)-like properties in gastric cancer cells via activating the interleukin-6 (IL-6)/IL-6 receptor (IL-6R)/signal transducer and activator of transcription 3 (STAT3) signaling. However, SFN could activate the microRNA-124 (miR-124), which directly targets the 3′-untranslated regions (UTR) of the IL-6R and STAT3. Moreover, knockdown of miR-124 eliminated the effects of SFN on CSC-like properties in GC cells, and in turn enhanced the anti-cancer effects of low-dose CDDP. These findings not only suggested a mechanism whereby SFN enhanced the anti-cancer functions of CDDP, but also helped to regard SFN as a potential chemotherapeutic factor in gastric cancer.

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RETRACTED ARTICLE: Down-regulated microRNA-124 expression as predictive biomarker and its prognostic significance with clinicopathological features in breast cancer patients

Cited by 10 publications

References 23 publications

MicroRNA-124 enhances response to radiotherapy in human epidermal growth factor receptor 2-positive breast cancer cells by targeting signal transducer and activator of transcription 3

MicroRNA-124 enhances response to radiotherapy in human epidermal growth factor receptor 2-positive breast cancer cells by targeting signal transducer and activator of transcription 3

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

Sulforaphane improves chemotherapy efficacy by targeting cancer stem cell-like properties via the miR-124/IL-6R/STAT3 axis

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