miR-203 Inhibits Frizzled-2 Expression via CD82/KAI1 Expression in Human Lung Carcinoma Cells

Mine, Mariko; Yamaguchi, Kojiro; Sugiura, Tetsuro; Chigita, Satomi; Yoshihama, Naoya; Yoshihama, Rumi; Hiyake, Naomi; Kobayashi, Yasuhiko; Mori, Yoshihide

doi:10.1371/journal.pone.0131350

Cited by 29 publications

(20 citation statements)

References 30 publications

(43 reference statements)

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“…CD82 downregulates the level of the transmembrane protein Frizzled, probably by enhancing miR-203 expression, and thereby reduces Wnt signaling [61,62]. CD82 also inhibits the expression of glycogen synthase kinase-3β (GSK-3β) and casein kinase 1α (CK1α), resulting in less phosphorylation and extranuclear accumulation of β-catenin [62].…”

Section: In Solid Tumor Cells Cd82 Regulates the Signaling Of Membramentioning

confidence: 99%

Tetraspanin CD82: a suppressor of solid tumors and a modulator of membrane heterogeneity

Feng

Huang

Wren

et al. 2015

Cancer Metastasis Rev

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Tetraspanin CD82 suppresses the progression and metastasis of a wide range of solid malignant tumors. However, its roles in tumorigenesis and hematopoietic malignancy remain unclear. Ubiquitously expressed CD82 restrains cell migration and cell invasion by modulating both cell-matrix and cell-cell adhesiveness and confining outside-in pro-motility signaling. This restraint at least contributes to, if not determines, the metastasis-suppressive activity and, also likely, the physiological functions of CD82. As a modulator of cell membrane heterogeneity, CD82 alters microdomains, trafficking, and topography of the membrane by changing the membrane molecular landscape. The functional activities of membrane molecules and the cytoskeletal interaction of the cell membrane are subsequently altered, followed by changes in cellular functions. Given its pathological and physiological importance, CD82 is a promising candidate for clinically predicting and blocking tumor progression and metastasis and also an emerging model protein for mechanistically understanding cell membrane organization and heterogeneity.

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Section: In Solid Tumor Cells Cd82 Regulates the Signaling Of Membramentioning

confidence: 99%

Tetraspanin CD82: a suppressor of solid tumors and a modulator of membrane heterogeneity

Feng

Huang

Wren

et al. 2015

Cancer Metastasis Rev

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“…The inhibition of KAI1 was related to EGFR over-expression, as well as EGFR mutations in non-small cell lung cancers (15). KAI1 suppress metastasis by inhibition of Wnt signaling pathway through up-regulation of miR-203 and directly down-regulation of FZD2 in lung cancer (16). Thus, it was accepted that KAI1 suppresses tumor metastasis via multiple signaling pathway and considered as a valuable marker for assessing metastasis potential (17).…”

Section: Introductionmentioning

confidence: 99%

Nm23-H1 was involved in regulation of KAI1 expression in high-metastatic lung cancer cells L9981

et al. 2016

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Background:The tetraspanin KAI1/CD82 was identified as a tumor metastasis suppressor that downregulated in malignant progression of lung cancer. However, the underlying mechanism of anti-metastasis role of KAI1 in lung cancer is hardly known. In this paper, we sought to study the function and regulatory mechanism of KAI1 in high metastasis lung cancer cell line.Methods: KAI1 expression was detected in high/low metastatic large lung cancer cell line L9981/NL9980 by quantitative real-time polymerase chain reaction (qRT-PCR). The tumor suppressor function of KAI1 was determined by wound healing assay after over-expression or knockdown of KAI1 in L9981 or NL9980 cells.Invasion assay was performed to detect the invasion ability of L9981 by transfection of KAI1. The effect of tumor suppressor p53 on KAI1 expression was measured by western blot and luciferase assay. Then the regulation of KAI1 due to over-expression of metastasis suppressor nm23-H1 was monitored by qRT-PCR, western blot and reporter gene assay. The progression of L9981 cells after p53 and nm23-H1 expression was detected by invasion assay. Also, methylation status of KAI1 promoter in NL9980 and L9981 cells were examined by bisulfite sequencing and methylation-specific PCR.Results: We found that KAI1 is down-regulated in high metastatic L9981 cells compare with NL9980 cells. The migration and invasion of L9981 cells were remarkably suppressed in vitro by KAI1 transfection.The migration ability of NL9980 was enhanced by inhibition of KAI1. Furthermore, KAI1 expression was induced after over-expression of p53 or nm23-H1, while cell invasion was inhibited in L9981 cells. The results of reporter analysis indicated that KAI1 promoter region between −922 to −846 could response to nm23-H1. In addition, we discovered only slight methylation of KAI1 promoter, which showed that loss expression of KAI1 in L9981 cells may not due to promoter methylation. Conclusions:The results suggested that nm23-H1 was involved in the KAI1-regulated inhibition of metastasis in lung cancer cells. More insights into the relationship between KAI1 and other metastasis suppressors will pave the way for the elucidation of anti-metastasis mechanism in lung cancer.

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“…Interestingly, Xu et al also found that this gene is a target of miR-34c in an osteosarcoma model [131]. Moreover, recent evidence suggests the targeting of the Wnt/β-catenin-related receptor, Frizzled-2, by miR-203, even if no direct binding was attested [139]. In addition, it was found that miR-203 indirectly increases the expression of the Dickkopf Wnt signaling pathway inhibitor 1 (DKK-1), a secreted Wnt-related pathway inhibitor reported to impede osteogenesis in MSCs [140].…”

Section: The Wnt Pathwaymentioning

confidence: 99%

Implication of the p53-Related miR-34c, -125b, and -203 in the Osteoblastic Differentiation and the Malignant Transformation of Bone Sarcomas

Jacques

Tesfaye

Lavaud

et al. 2020

Cells

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The formation of the skeleton occurs throughout the lives of vertebrates and is achieved through the balanced activities of two kinds of specialized bone cells: the bone-forming osteoblasts and the bone-resorbing osteoclasts. Impairment in the remodeling processes dramatically hampers the proper healing of fractures and can also result in malignant bone diseases such as osteosarcoma. MicroRNAs (miRNAs) are a class of small non-coding single-strand RNAs implicated in the control of various cellular activities such as proliferation, differentiation, and apoptosis. Their post-transcriptional regulatory role confers on them inhibitory functions toward specific target mRNAs. As miRNAs are involved in the differentiation program of precursor cells, it is now well established that this class of molecules also influences bone formation by affecting osteoblastic differentiation and the fate of osteoblasts. In response to various cell signals, the tumor-suppressor protein p53 activates a huge range of genes, whose miRNAs promote genomic-integrity maintenance, cell-cycle arrest, cell senescence, and apoptosis. Here, we review the role of three p53-related miRNAs, miR-34c, -125b, and -203, in the bone-remodeling context and, in particular, in osteoblastic differentiation. The second aim of this study is to deal with the potential implication of these miRNAs in osteosarcoma development and progression.

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miR-203 Inhibits Frizzled-2 Expression via CD82/KAI1 Expression in Human Lung Carcinoma Cells

Cited by 29 publications

References 30 publications

Tetraspanin CD82: a suppressor of solid tumors and a modulator of membrane heterogeneity

Tetraspanin CD82: a suppressor of solid tumors and a modulator of membrane heterogeneity

Nm23-H1 was involved in regulation of KAI1 expression in high-metastatic lung cancer cells L9981

Implication of the p53-Related miR-34c, -125b, and -203 in the Osteoblastic Differentiation and the Malignant Transformation of Bone Sarcomas

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