Microenvironment regulates the expression of miR-21 and tumor suppressor genes PTEN, PIAS3 and PDCD4 through ZAP-70 in chronic lymphocytic leukemia

Carabia, Júlia; Carpio, Cecilia; Abrisqueta, Pau; Jiménez, Isabel; Purroy, Noelia; Calpe, Eva; Palacio, Carles; Bosch, Francesc; Crespo, Marta

doi:10.1038/s41598-017-12135-7

Cited by 29 publications

(26 citation statements)

References 35 publications

(45 reference statements)

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“…Furthermore, phosphorylation levels of MAPK were significantly reduced in pcDNA3.1-CIC groups but increased in CIC-shRNA groups when compared with controls, indicating that CIC silencing activated the MAPK signaling pathway (Figure 7). Collectively, these results suggested that the regulation of renal carcinoma invasion and proliferation by CIC may occur through its activation of the MAPK signaling pathway, in a similar manner to that previously described as BANCR 32 and PTEN 33 and so on.…”

Section: Cic Silencing Promoted Proliferation Invasion Of Rcc Cells supporting

confidence: 74%

<p>miR-106b promotes proliferation and invasion by targeting Capicua through MAPK signaling in renal carcinoma cancer</p>

Miao¹,

Shu²,

Zhuang³

et al. 2019

OTT

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Background: miR-106b has been reported to play a vital role in pathogenesis of some types of cancer, whilst the role of miR-106b in renal carcinoma cancer (RCC) remains unknown. Purpose: The objective of this study was to identify the mechanism of miR-106b regulating the progression of renal carcinoma. Method: The expression of miR-106b was analyzed in RCC cell lines, RCC and adjacent normal renal tissues through qRT-PCR assays. Target mRNA of miR-106b was predicted with databases and verified by luciferase reporter assays. And the effects of miR-106b or targeted mRNA on cell proliferation, invasion, the process of epithelial-mesenchymal transitions (EMTs) were assessed in vitrothrough CCK-8, transwell cell invasion assays, qRT-PCR and Western blotting assays respectively. In addition, the effects of miR-106b on the growth of xenografts mice were analyzedin vivo. Results: The results demonstrated that miR-106b was significantly increased both in RCC tissues and cell lines. Luciferase reporter assays revealed that miR-106b inhibited Capicua expression by targeting its 3ʹ-UTR sequence. And miR-106b promoted cell proliferation, invasion, EMT progression in RCC cellin vitro, as well as promoted the tumor growth of 786-O cells derived xenografts mice. Additionally, loss of Capicua promoted the activation of MAPK signaling pathway. Conclusion: The study suggested that miR-106b regulated RCC progression through MAPK signaling pathway partly by targeting Capicua, which might provide valuable evidence for therapeutic target development of RCC.

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Section: Cic Silencing Promoted Proliferation Invasion Of Rcc Cells supporting

confidence: 74%

<p>miR-106b promotes proliferation and invasion by targeting Capicua through MAPK signaling in renal carcinoma cancer</p>

Miao¹,

Shu²,

Zhuang³

et al. 2019

OTT

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“…We also demonstrated that miR-21 represents one of the most abundant miRs transported within EV cargos secreted by oral cancer cells and that CSC_EVs contained a significantly higher level of miR-21 than their parental counterparts. This is of translational relevance, considering that miR-21 is a well-established oncogenic miR whose major targets include the tumor suppressors PTEN and PDCD4 [30,31], both of which inhibit PI3K/AKT/mTOR signaling and the Wnt/β-catenin cascade [30,32]. Moreover, EV miR-21 was implicated in resistance of recipient cancer cells to anticancer therapeutics [12,33]; in agreement, our bioinformatics analysis showed that miR-21 was the most abundant miR encapsulated within salivary EVs from six patients with OSCC.…”

Section: Discussionmentioning

confidence: 99%

Ovatodiolide Suppresses Oral Cancer Malignancy by Down-Regulating Exosomal Mir-21/STAT3/β-Catenin Cargo and Preventing Oncogenic Transformation of Normal Gingival Fibroblasts

Chen

Bamodu

et al. 2019

Cancers

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Oral squamous cell carcinoma (OSCC) is among the most commonly diagnosed malignancies in the world. Patients with OSCC often develop treatment resistance, resulting in a poor prognosis. Mounting evidence indicates that interactions between cancerous cells and other components of the tumor microenvironment (TME) determine their response to treatment. Herein, we examined the role of cancer stem cell-derived extracellular vesicles (CSC_EVs) generated from CAL27 and SCC-15 OSCC cells in the development of cisplatin (CDDP) resistance. We demonstrated that CSC_EVs enhance CDDP resistance, clonogenicity, and the tumorsphere formation potential of OSCC cells. Our bioinformatics analyses revealed that OSCC_EVs are enriched with microRNA (miR)-21-5p and are associated with increased metastasis, stemness, chemoresistance, and poor survival in patients with OSCC. Mechanistically, enhanced activity of CSC_EVs was positively correlated with upregulated Cancers 2020, 12, 56 2 of 16 β-catenin, phosphatidylinositol-3 kinase (PI3K), signal transducer and activator of transcription 3 (STAT3), mammalian target of rapamycin (mTOR), and transforming growth factor (TGF)-β1 messenger (m)RNA and protein expression levels. CSC_EVs also conferred a cancer-associated fibroblast (CAF) phenotype on normal gingival fibroblasts (NGFs), with the resultant CAFs enhancing the oncogenicity of OSCC cells. Interestingly, treatment with ovatodiolide (OV), the bioactive component of Anisomeles indica, suppressed OSCC tumorigenesis by reducing the cargo content of EVs derived from CSCs, suppressing self-renewal, and inhibiting the NGF-CAF transformation by disrupting EV-TME interactions. Moreover, by suppressing miR-21-5p, STAT3, and mTOR expressions in CSC_EVs, OV re-sensitized CSCs to CDDP and suppressed OSCC tumorigenesis. In vivo, treatment with OV alone or in combination with CDDP significantly reduced the tumor sphere-forming ability and decreased EV cargos containing mTOR, PI3K, STAT3, β-catenin, and miR-21-5p. In summary, our findings provide further strong evidence of OV's therapeutic effect in OSCC.

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“…Moreover, 10 hub genes were identified in total, 4 of them were related to survival, namely ZAP70, AGMAT, AKR1C1 and AKR1C3. Studies have shown that ZAP70 is involved in the development of chronic lymphocytic leukemia 27 . AGMAT could promote the lung adenocarcinoma tumorigenesis by activating the NO-MAPKs-PI3K/ Akt pathway 28 .…”

Section: Discussionmentioning

confidence: 99%

Effects and mechanisms of AMIGO2 in proliferation, migration and drug resistance of bladder cancer

Han

Xiong

Zhang

et al. 2020

Preprint

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Background Bladder cancer is the most common malignancy in urinary system, but the therapeutic targets remain elusive. This study aims to reveal the relationship between AMIGO2 and proliferation, migration, drug-resistance and tumorigenicity of bladder cancer, and explore the potential molecular mechanisms. Methods The expression of AMIGO2 in human bladder cancer tissues is measured by qRT-PCR and immunohistochemistry (IHC). Stable AMIGO2 knockdown cell lines T24 and 5637 were established by lentivirus transfection. Cell viability assay (CCK-8 assay) was used to determine cell proliferation, flow cytometry analysis was utilized to detect cell cycle, and wound healing assay was proceeded to test migration ability of bladder cancer cells. Chemosensitivity to cisplatin was measured by CCK-8 assay. Xenograft mouse model was established for investigating the effect of AMIGO2 on tumor formation in vivo. The RNA Sequencing technology was used to explore differentially expressed genes (DEGs) between knockdown group and negative control group of T24. Bioinformatics analysis upon the results of RNA-Seq was proceeded to understand underlying mechanisms. Results AMIGO2 was upregulated in bladder cancer cells and tissues. Inhibited expression of AMIGO2 suppresses cell proliferation and migration, which might be mediated by cell cycle arrest in G1 phase. AMIGO2 could reduce chemoresistance to cisplatin in bladder cancer cells. Low AMIGO2 expression inhibited tumorigenicity of T24 in nude mice. 917 DEGs were identified by RNA-Sequencing technology and bioinformatics analysis. The DEGs were mainly enriched in cell-cell adhesion, ATP-binding cassette transporters (ABC transporters), PPAR signaling pathway and some other pathways. Among ten hub genes, four of them might be associated with the prognosis of bladder cancer patients. Conclusion AMIGO2 is overexpressed in bladder cancer cells and tissues and serves as an oncogene in bladder cancer. It also reduces chemoresistance to cisplatin. The process might be regulated by particular pathways including ABC transporters and PPAR signaling pathway. Four hub genes might be associated with prognosis of bladder cancer patients.

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Microenvironment regulates the expression of miR-21 and tumor suppressor genes PTEN, PIAS3 and PDCD4 through ZAP-70 in chronic lymphocytic leukemia

Cited by 29 publications

References 35 publications

<p>miR-106b promotes proliferation and invasion by targeting Capicua through MAPK signaling in renal carcinoma cancer</p>

<p>miR-106b promotes proliferation and invasion by targeting Capicua through MAPK signaling in renal carcinoma cancer</p>

Ovatodiolide Suppresses Oral Cancer Malignancy by Down-Regulating Exosomal Mir-21/STAT3/β-Catenin Cargo and Preventing Oncogenic Transformation of Normal Gingival Fibroblasts

Effects and mechanisms of AMIGO2 in proliferation, migration and drug resistance of bladder cancer

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