miRNA-205 Is a Candidate Tumor Suppressor that Targets ZEB2 in Renal Cell Carcinoma

Chen, Zhi; He, Yao; Liu, Longfei; Li, Dongjie; Chen, Xiang

doi:10.1159/000368792

Cited by 40 publications

(30 citation statements)

References 27 publications

(42 reference statements)

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“…We also confirmed that miR-200c expression decreased ZEB1 level in VRCs [53], but we did not observe any effect on miR-200c on ZEB2 expression [54]. VRCs overexpressed miR-205 shown ZEB1/2 downregulation in cancer cells, what is in accordance with previous works [55,56]. Our results, suggests that the molecular mechanisms of miR-200 family on EMT might be cell type specific and more work needs to be done to clarify this.…”

Section: Discussionsupporting

confidence: 92%

Genetical engineered lung cancer cell for analyzing Epithelial-Mesenchymal transition

Kiełbus

Czapiński

Kałafut

et al. 2019

Preprint

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Cell plasticity, defined as the ability to undergo phenotypical transformation in a reversible 12 manner, is a physiological processes that also exert important roles in disease progression Two forms 13 of cellular plasticity are epithelial-mesenchymal transition (EMT) and its inverse process, 14 mesenchymal-epithelial transition (MET). These processes have been correlated to the poor outcome 15 of different types of neoplasias as well as drug resistance development. Since EMT/MET are 16 transitional processes, we have generated and validated a reporter cell line. Specifically, a far-red 17 fluorescent protein was knocked-in in-frame with the mesenchymal gene marker VIMENTIN (VIM) 18 in H2170 lung cancer cells. The vimentin reporter cells (VRCs) are a reliable model for studying EMT 19 and MET showing cellular plasticity upon a series of stimulations. These cells are a robust platform 20 to dissect the molecular mechanisms of these processes, and for drug discovery in vitro and in the 21 future in vivo.22 Keywords: epithelial-mesenchymal transition (EMT); mesenchymal-epithelial transition (MET); 23 cancer cell line; vimentin; reporter; 24 25 29 transition (EMT) and mesenchymal-epithelial transition (MET), respectively. EMT has been 30 correlated to the metastasis and invasion potential of many types of malignancies [2]. The fact that 31 the poor outcome of many types of neoplasias correlates with EMT/MET, makes these molecular 32 phenomena important focus for research and drug targeting [3-6]. Despite the clinical association,33 the role of EMT/MET in metastasis is inconclusive, for example mesenchymal-like prostate cancer 34 cells survive in circulation but, unlike epithelial or cells undergoing EMT, they are unable to form 35 macrometastases [7]. In fact, breast cancer cell metastasis to lung tissue in mice was not affected by36 decreasing EMT -by targeting EMT-triggering transcription factors such as SNAI1 (Snail) and SNAI2 37 (Slug) by overexpressing miR-200 [8]. An additional role of EMT in tumorigenesis might be the 38 development of apoptotic tolerance and increased resistance to chemotherapy as has been found in 39animal models and patients [8,9]. Recently, a hybrid stage between epithelial and mesenchymal 40 2 of 19 phenotypes (hybE/M) has been recognized, and such hybE/M cells migrate outside the primary 41 tumors displaying some mesenchymal features such as spindle-like morphology, increased nuclear 42 levels of ZEB1 transcription factor, and epithelial ones such as cell-cell adhesion potential [10,11]. 43In order to study the transitory stages of EMT, MET and hybE/M, in particular at in vivo settings, 44 there is need to generate reporter cells to visualize phenotypical changes. There have been different 45 approaches to this, for example the use of heterologous fluorescent proteins driven under stage-46 specific promoters such as mesenchymal (ZEB1) and epithelial (CDH1) [12], mesenchymal snai1 and 47 epithelial sox10 in zebrafish [13], or mesenchymal Vimentin (Vim) in mice [14]. Nevertheless, 48 hete...

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Section: Discussionsupporting

confidence: 92%

Genetical engineered lung cancer cell for analyzing Epithelial-Mesenchymal transition

Kiełbus

Czapiński

Kałafut

et al. 2019

Preprint

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“…It has been well-established that miRs play important roles in the regulation of cell proliferation, differentiation, apoptosis, migration, invasion, and so forth (9–11). Moreover, many miRs have been reported to direct target oncogenes or tumor suppressors, and thus play suppressive or promoting roles in human cancers (10,12–14).…”

Section: Introductionmentioning

confidence: 99%

miR-663b promotes tumor cell proliferation, migration and invasion in nasopharyngeal carcinoma through targeting TUSC2

Liang

Zhang

Deng

et al. 2017

Experimental and Therapeutic Medicine

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The authors' previous study revealed that the serum levels of microRNA (miR)-663b are significantly increased in patients with nasopharyngeal carcinoma (NPC), and are associated with NPC progression and poor prognosis. However, the molecular mechanism of underlying NPC growth and metastasis remains unclear. In the present study, quantitative polymerase chain reaction and western blot analyses were performed to examine changes to mRNA and protein expression, respectively. MTT, wound healing and Transwell assays were used to examine cell proliferation, migration and invasion, respectively. Luciferase reporter gene assays were performed to identify target genes of miR-663b. It was demonstrated that miR-663b was significantly upregulated in NPC tissue compared with non-tumor nasopharyngeal epithelial tissue samples. Furthermore, miR-663b expression gradually increased with advancing stages of NPC, with the highest expression being observed in the latest stage IV. The increased expression of miR-663b was associated with advanced clinical stage and lymph node metastasis. In addition, miR-663b expression was increased in NPC cell lines compared with normal nasopharyngeal epithelial NP69 cells. Knockdown of miR-663b resulted in a significant reduction in the proliferation, migration and invasion of NPC CNE1 cells. Tumor suppressor candidate 2 (TUSC2) was identified as a novel target gene of miR-663b. It was further demonstrated that TUSC2 was significantly downregulated in NPC tissue samples and cell lines. miR-663b negatively regulated the expression of TUSC2 at the post-transcriptional level in CNE1 cells. Additionally, inhibition of TUSC2 expression attenuated the suppressive effects of miR-663b downregulation on the proliferation, migration and invasion of CNE1 cells. To the best of our knowledge, this is the first study to demonstrate that miR-663b, which is upregulated in NPC, promotes the proliferation, migration and invasion of NPC cells, partially through the inhibition of TUSC2 expression. Therefore, it is suggested that miR-663b is a promising therapeutic target for the treatment of patients with NPC.

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“…Therefore, alteration in miRNA expression is considered to have a part in cancer initiation and progression through regulating the expression of various oncogenes and tumor suppressive genes [7]. It has been reported that miRNA-451a is associated with cell proliferation, migration, and apoptosis in RCC [8], and miRNA-205 is a candidate tumor suppressor by targeting ZEB2 in RCC [9]. Another member of the miRNA family, miR-106a*, is found downregulated in follicular lymphoma [10], but there is no report on its role in RCC.…”

Section: Introductionmentioning

confidence: 99%

miR-106a* inhibits the proliferation of renal carcinoma cells by targeting IRS-2

Zhang

et al. 2015

Tumor Biol.

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MicroRNAs play critical roles in the development and progression of human cancers. Although it has been reported that miR-106a* is downregulated in follicular lymphoma, its role in renal cell carcinoma (RCC) remains unknown. This study investigated the expression and role of miR-106a* in human RCC. Our results showed that the miR-106a* expression decreased dramatically in clinical RCC tissues and cell lines. In vitro, overexpression of miR-106a* suppressed RCC cell proliferation and S/G2 transition, whereas inhibition of miR-106a* promoted cell proliferation and S/G2 transition. It was also found that miR-106a* expression was inversely correlated with the expression of insulin receptor substrate 2 (IRS-2). IRS-2 was determined to be a direct target of miR-106a* by a luciferase reporter assay. Importantly, silencing IRS-2 resulted in the same biologic effects as those of miR-106a* overexpression in RCC cells, including inhibition of RCC cell proliferation and triggering of S/G2 cell cycle arrest with inhibition of the PI3K/Akt signaling pathway. These results indicate that miR-106a* affects RCC progression by targeting IRS-2 with suppression of the PI3K/Akt signaling pathway in RCC cells. The findings suggest miR-106a* as a novel strategy for RCC treatment.

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miRNA-205 Is a Candidate Tumor Suppressor that Targets ZEB2 in Renal Cell Carcinoma

Cited by 40 publications

References 27 publications

Genetical engineered lung cancer cell for analyzing Epithelial-Mesenchymal transition

Genetical engineered lung cancer cell for analyzing Epithelial-Mesenchymal transition

miR-663b promotes tumor cell proliferation, migration and invasion in nasopharyngeal carcinoma through targeting TUSC2

miR-106a* inhibits the proliferation of renal carcinoma cells by targeting IRS-2

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