MiroRNA-188 Acts as Tumor Suppressor in Non-Small-Cell Lung Cancer by Targeting MAP3K3

Zhao, Lili; Ni, Xin; Zhao, Linlin; Zhang, Yao; Jin, Dayong; Yin, Wei; Wang, Dandan; Zhang, Wei

doi:10.1021/acs.molpharmaceut.8b00071

Cited by 39 publications

(40 citation statements)

References 47 publications

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“…Furthermore, we found that IL6ST is a functional target gene mediating the ability of miR‐188‐5p to regulate cellular proliferation and migration. Previously, many other genes including FGF5 (Fang et al, ), MAP3K3 (Zhao et al, ), and UBE2I (Zhang et al, ) have been identified as targets of miR‐188‐5p in hepatocellular carcinoma, lung cancer, and prostate cancer, respectively. As compared with these previously validated targets, IL6ST may be a more important signaling molecule widely linked with cancer development and progression.…”

Section: Discussionmentioning

confidence: 99%

miR‐188‐5p suppresses cellular proliferation and migration via IL6ST: A potential noninvasive diagnostic biomarker for breast cancer

Wang

Zhang

Yang

et al. 2019

Journal Cellular Physiology

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Previously, serum miR-188-5p is differentially expressed in breast cancer, but the diagnostic potential of circulating miR-188-5p as well as its regulatory mechanism in breast cancer remain uncertain. Herein, serum miR-188-5p was detected by real-time polymerase chain reaction in patients with breast cancer, breast fibroadenoma, and healthy subjects.Circulating miR-188-5p was abnormally elevated in patients with breast cancer as compared with these other two groups, and was reduced in patients with breast cancer following surgical treatment. Increased serum miR-188-5p corresponded to lymph node metastasis status and TNM stages of breast cancer. A receiver operating characteristic curve analysis of the ability to circulate miR-188-5p to distinguish between patients with breast cancer and either noncancerous patients or patients with breast fibroadenoma yielded corresponding areas under the curve of 0.894 and 8.814. miR-188-5p was downregulated in the highly malignant cancer line MDA-MB-231 relative to the less malignant MCF-7 cells. In vitro, functional analyses conducted via transfecting cells with mimics and inhibitors revealed miR-188-5p to suppress breast cancer cell proliferation and migration, which was mediated by its downstream target IL6ST. Comparison of intracellular and exosomal miR-188-5p levels indicated that miR-188-5p was selectively sorted into exosomes derived from MDA-MB-231 cells rather than those from MCF-7 cells. However, exosomal miR-188-5p levels in the serum of patients with breast cancer were reduced compared to healthy controls and did not differ relative to patients with breast fibroadenoma. In summary, miR-188-5p acts in a tumor-suppressive manner in breast cancer progression and may serve as a noninvasive early diagnostic biomarker and therapeutic target in breast cancer.

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Section: Discussionmentioning

confidence: 99%

miR‐188‐5p suppresses cellular proliferation and migration via IL6ST: A potential noninvasive diagnostic biomarker for breast cancer

Wang

Zhang

Yang

et al. 2019

Journal Cellular Physiology

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“…Greater than seventy percent Wee1 knockdown was achieved in both cell lines ( Figure 3F). Interestingly, depletion of MAP3K3, known to promote ovarian and NSCLC tumor growth (31,32), inhibited PDGFRAmutant GIST cell viability, however no selective small molecule inhibitors are currently available to explore targeting MAP3K3 in GIST. Overexpression of Wee1 has also been observed in numerous malignancies, including breast and melanoma (33).…”

Section: Mapping the Distinct Kinome Signatures Among Gist Subtypesmentioning

confidence: 99%

Identification of Wee1 as Target in Combination with Avapritinib for the Treatment of Gastrointestinal Stromal Tumor

Sharipova

Kozinova

et al. 2020

Preprint

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Gastrointestinal stromal tumor (GIST) management has been revolutionized by the identification of activating mutations in KIT and PDGFRA and clinical application of receptor tyrosine kinase (RTK) inhibitors in advanced disease. Stratification of GIST into molecularly defined subsets provides insight into clinical behavior and response to approved targeted therapies. Although these RTK inhibitors are effective in most GIST, resistance remains a significant clinical obstacle.Development of effective strategies for refractory GIST requires identification of novel targets to provide additional therapeutic options. Global kinome profiling has potential to identify critical signaling networks and reveal protein kinases that are essential in GIST. Using Multiplexed Inhibitor Beads and Mass Spectrometry paired with a super-SILAC kinome standard, we explored the majority of the kinome in GIST specimens from the three most common molecular subtypes to identify novel kinase targets. Kinome profiling revealed distinct signatures in GIST subtypes.PDGFRA-mutant GIST had elevated tumor associated macrophage (TAM) kinases and immunohistochemical analysis confirmed increased TAMs present in these tumors. Kinome profiling with loss-of-function assays revealed a significant role for G2-M tyrosine kinase, Wee1, in GIST survival. In vitro and in vivo studies revealed significant efficacy of MK-1775 (Wee1 inhibitor) in combination with avapritinib in KIT and PDGFRA-mutant GIST cell lines, and notable efficacy of MK-1775 as a monotherapy in the PDGFRA-mutant line. These studies provide strong preclinical justification for the use of MK-1775 in GIST.

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“…Previous studies showed that miR-188 expression was signi cantly down-regulated at the tumor sites and cancer cells [19]. In vitro transfection of miR-188 reduced cell proliferation and migration potential and promoted cell apoptosis [13]. In xenograft model, miR-188 inhibited tumor growth derived from cancer cells [13].…”

Section: Introductionmentioning

confidence: 96%

“…Therefore, miRNA-based gene therapy provides an attractive anti-tumor approach for integrated cancer therapy [10,11]. miR-188 has been shown to be down-regulated in various types of cancer, such as cervical cancer [12], non-small cell lung cancer [13], gastric cancer [14], glioma [15], coloretal cancer [16], oral squamous cell carcinoma [17], hepatocellular carcinoma [18], prostate cancer [19], acute myeloid leukemia [20] and rectal cancer [21]. Previous studies showed that miR-188 expression was signi cantly down-regulated at the tumor sites and cancer cells [19].…”

Section: Introductionmentioning

confidence: 99%

“…In vitro transfection of miR-188 reduced cell proliferation and migration potential and promoted cell apoptosis [13]. In xenograft model, miR-188 inhibited tumor growth derived from cancer cells [13]. In colon cancer, miR-188-3p has been shown as a novel independent prognostic factor in colorectal cancer patients, which can be partly explained by its effect on MLLT4 expression and migration of cancer cells [16].…”

Section: Introductionmentioning

confidence: 99%

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miR-188 promotes Oxaliplatin resistances through targeting RASA1 in colon cancer cells

Zhu

Luo

Song

et al. 2020

Preprint

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Background: One main drawback of chemotherapy application in colon cancer clinically is drug resistance. miR-188-5p has been shown to be down-regulated in various types of cancer. The aim of this study was to explore the molecular mechanism of miR-188-5p in drug resistant cancer cells. Methods: we examined the effects of miR-188-5p on the sensitivity of colon cancer cells to oxaliplatin (OXA) by using SW480/OXA cell line. The target of miR-188-5p was determined by luciferase activity assay. The cell cycle distribution were detected by flow cytometry. The expression of p21, Hoechst 33342 staining and Annexin V assays were used to detect the cell apoptosis. Results: The expression of miR-188-5p was significantly increased in SW480/OXA cells compared with SW480 cells. By luciferase assay we found that miR-188-5p miRNA binds to RASA1 (Ras GTPase-activating protein 1, also known as p120RasGAP), and overexpression of miR-188-5p inhibited RASA1 expression by binding to the 3'-untranslated region of RASA1 mRNA. In addition, suppression of miR-188-5p enhanced the chemosensitivity of the oxaliplatin-resistant colon cancer cells. Furthermore, suppression of RASA1 abrogated the increasement of cell apoptosis induced by miR-188-5p inhibitor, while, overexpression of RASA1 induced cell apoptosis in SW480/OXA cells. Our results suggested that miR-188-5p played chemoresistant role in colon cancer through regulating RASA1 expression. Conclusion: The findings of our study suggest that target miR-188-5p is capable of enhancing the chemosensitivity of colon cancer cells by promoting RASA1.

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MiroRNA-188 Acts as Tumor Suppressor in Non-Small-Cell Lung Cancer by Targeting MAP3K3

Cited by 39 publications

References 47 publications

miR‐188‐5p suppresses cellular proliferation and migration via IL6ST: A potential noninvasive diagnostic biomarker for breast cancer

miR‐188‐5p suppresses cellular proliferation and migration via IL6ST: A potential noninvasive diagnostic biomarker for breast cancer

Identification of Wee1 as Target in Combination with Avapritinib for the Treatment of Gastrointestinal Stromal Tumor

miR-188 promotes Oxaliplatin resistances through targeting RASA1 in colon cancer cells

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