<i>miR-381</i> suppresses C/EBPα-dependent Cx43 expression in breast cancer cells

Jia, Ming; Zhou, Yan; Du, Junze; Fan, Shenghao; Pan, Beibei; Wang, Yinhuan; Fan, Lingjun; Jiang, Jun

doi:10.1042/bsr20150167

Cited by 40 publications

(36 citation statements)

References 39 publications

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“…However, the reported expression patterns and roles of miR-381 in various types of cancer markedly differ. miR-381 has been shown to be downregulated in malignancies and exerts tumour suppressive effects on colon, breast and liver cancer and pituitary tumours (27,(37)(38)(39). In lung cancer, this miRNA has been shown to inhibit cell migration and invasion by targeting LRH-1, where it acts as a prognostic marker (40).…”

Section: Discussionmentioning

confidence: 99%

miR‑381 and miR‑489 suppress cell proliferation and invasion by targeting CUL4B via the Wnt/β‑catenin pathway in gastric cancer

et al. 2018

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Accumulating evidence has highlighted the critical role of cullin 4B (CUL4B) in driving tumourigenesis in several malignancies, including gastric cancer (GC); however, the mechanisms underlying CUL4B upregulation remain unclear. The dysregulation of microRNAs (miRNAs or miRs) is known to be involved in tumourigenesis. In this study, we report that the expression of miR-381 and miR-489 is downregulated and is negatively correlated with that of CUL4B in GC tissues and cell lines. Further analysis verified that miR-381 and miR-489 directly targeted CUL4B. CUL4B silencing inhibited cell proliferation, migration and invasion by inactivating the Wnt/β-catenin pathway. miR-381/miR-489 overexpression recapitulated the effects of CUL4B silencing, while CUL4B restoration negated the suppressive effects induced by the ectopic expression of miR-381/miR-489. Furthermore, miR-381/miR-489 exerted tumour suppressive functions by inactivating the Wnt/β-catenin pathway through the targeting of CUL4B. Taken together, the findings of this study suggest that the miR-381/miR-489-mediated expression of CUL4B modulates the proliferation and invasion of GC cells via the Wnt/β-catenin pathway, which indicates that the miR-381/miR-489-CUL4B axis is critical in the control of GC tumourigenesis.

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Section: Discussionmentioning

confidence: 99%

miR‑381 and miR‑489 suppress cell proliferation and invasion by targeting CUL4B via the Wnt/β‑catenin pathway in gastric cancer

et al. 2018

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“…Although functional C/EBPa mutations have not been found in solid tumors, C/EBPa levels are found down-regulated in various types of cancer, indicating that inactivation of C/EBPa might be a requirement for tumor development (Lourenco & Coffer, 2017). In contrast, some studies performed in hepatocellular carcinomas and breast cancer cells have shown that increased expression of C/EBPa correlated with increased proliferation and disease progression (Tomizawa et al, 2007;Lu et al, 2010;Ming et al, 2015). However, the mechanism by which C/EBPa fulfills this function in hormone-dependent processes and in particular in breast cancer cells is unknown.…”

Section: Introductionmentioning

confidence: 99%

C/EBPα mediates the growth inhibitory effect of progestins on breast cancer cells

et al. 2019

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Steroid hormones are key gene regulators in breast cancer cells. While estrogens stimulate cell proliferation, progestins activate a single cell cycle followed by proliferation arrest. Here, we use biochemical and genome‐wide approaches to show that progestins achieve this effect via a functional crosstalk with C/EBPα. Using ChIP‐seq, we identify around 1,000 sites where C/EBPα binding precedes and helps binding of progesterone receptor (PR) in response to hormone. These regions exhibit epigenetic marks of active enhancers, and C/EBPα maintains an open chromatin conformation that facilitates loading of ligand‐activated PR. Prior to hormone exposure, C/EBPα favors promoter–enhancer contacts that assure hormonal regulation of key genes involved in cell proliferation by facilitating binding of RAD21, YY1, and the Mediator complex. Knockdown of C/EBPα disrupts enhancer–promoter contacts and decreases the presence of these architectural proteins, highlighting its key role in 3D chromatin looping. Thus, C/EBPα fulfills a previously unknown function as a potential growth modulator in hormone‐dependent breast cancer.

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“…Afterward, miR-381 has been found to acts as a tumor suppressor in multiple cancer types such as gastric cancer (Cao et al, 2017), colon cancer (Liang et al, 2015), and prostate cancer (Formosa et al, 2014). Recent studies showed that low miR-381 expression was associated with metastasis of breast cancer (Ming et al, 2015;Xue et al, 2016). However, the relationship between miR-381 and DDP resistance of breast cancer has not been well elucidated.…”

Section: Introductionmentioning

confidence: 99%

miR‐381 overcomes cisplatin resistance in breast cancer by targeting MDR1

Wang

et al. 2018

Cell Biology International

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Increasing evidence suggests the involvement of microRNA-381 (miR-381) in chemoresistance of cancer treatment. However, its function and molecular mechanisms in breast cancer chemoresistance are still not well elucidated. In the present study, we aimed to investigate the functional role of miR-381 in cisplatin (DDP) resistance of breast cancer and discover the underlying molecular mechanism. The expression levels of miR-381 and MDR1 were detected by quantitative real-time PCR (qRT-PCR) and Western blot analysis in breast cancer tissues and cell lines. The DDP sensitivity and cell apoptosis of breast cancer cells were determined by MTT assay and flow cytometric analysis, respectively. The relationship between miR-381 and MDR1 was explored by target prediction and luciferase reporter analysis. miR-381 was decreased in DDP-resistant breast cancer tissues and cell lines. Low miR-381 expression was correlated with poor prognosis of breast cancer patients. miR-381 overexpression improved DDP sensitivity of MCF-7/DDP and MDA-MB-231/DDP cells. Conversely, miR-381 inhibition lowered the response of MCF-7 and MDA-MB-231 to DPP. Moreover, miR-381 could directly suppress multidrug resistance 1 (MDR1) expression. MDR1 knockdown could overcome DDP resistance in MCF-7/DDP and MDA-MB-231/DDP cells, while MDR1 overexpression led to DDP resistance in MCF-7 and MDA-MB-231 cells. Notably, MDR1 overexpression counteracted the inductive effect of miR-381 mimics on DDP sensitivity of MCF-7/DDP and MDA-MB-231/DDP cells. On the contrary, miR-381 inhibition-mediated DDP resistance in MCF-7 and MDA-MB-231 cells was reversed by MDR1 knockdown. In summary, miR-381 could overcome DDP resistance of breast cancer by directly targeting MDR1, providing a novel therapeutic target for breast cancer chemoresistance.

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miR-381 suppresses C/EBPα-dependent Cx43 expression in breast cancer cells

Abstract: miR-381 suppressed CX43 expression by directly targeting the 3′-UTR of C/EBPα, a novel transcription factor of Cx43 in human breast cancer cells. The miR-381–Cx43 axis might be a useful diagnostic and therapeutic target of metastatic breast cancer.

Cited by 40 publications

References 39 publications

miR‑381 and miR‑489 suppress cell proliferation and invasion by targeting CUL4B via the Wnt/β‑catenin pathway in gastric cancer

miR‑381 and miR‑489 suppress cell proliferation and invasion by targeting CUL4B via the Wnt/β‑catenin pathway in gastric cancer

C/EBPα mediates the growth inhibitory effect of progestins on breast cancer cells

miR‐381 overcomes cisplatin resistance in breast cancer by targeting MDR1

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