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  • 1
    In: Genes, MDPI AG, Vol. 13, No. 7 ( 2022-07-09), p. 1225-
    Abstract: Analysis of microRNA (miRNA) expression signatures in head and neck squamous cell carcinoma (HNSCC) has revealed that the miR-30 family is frequently downregulated in cancer tissues. The Cancer Genome Atlas (TCGA) database confirms that all members of the miR-30 family (except miR-30c-5p) are downregulated in HNSCC tissues. Moreover, low expression of miR-30e-5p and miR-30c-1-3p significantly predicts shorter survival of HNSCC patients (p = 0.0081 and p = 0.0224, respectively). In this study, we focused on miR-30e-5p to investigate its tumor-suppressive roles and its control of oncogenic genes in HNSCC cells. Transient expression of miR-30e-5p significantly attenuated cancer cell migration and invasive abilities in HNSCC cells. Nine genes (DDIT4, FOXD1, FXR1, FZD2, HMGB3, MINPP1, PAWR, PFN2, and RTN4R) were identified as putative targets of miR-30e-5p control. Their expression levels significantly predicted shorter survival of HNSCC patients (p 〈 0.05). Among those targets, FOXD1 expression appeared to be an independent factor predicting patient survival according to multivariate Cox regression analysis (p = 0.049). Knockdown assays using siRNAs corresponding to FOXD1 showed that malignant phenotypes (e.g., cell proliferation, migration, and invasive abilities) of HNSCC cells were significantly suppressed. Overexpression of FOXD1 was confirmed by immunostaining of HNSCC clinical specimens. Our miRNA-based approach is an effective strategy for the identification of prognostic markers and therapeutic target molecules in HNSCC. Moreover, these findings led to insights into the molecular pathogenesis of HNSCC.
    Type of Medium: Online Resource
    ISSN: 2073-4425
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527218-4
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  • 2
    Online Resource
    Online Resource
    MDPI AG ; 2019
    In:  International Journal of Molecular Sciences Vol. 20, No. 6 ( 2019-03-20), p. 1406-
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 20, No. 6 ( 2019-03-20), p. 1406-
    Abstract: As hepatocellular carcinoma (HCC) usually occurs in the background of cirrhosis, which is an end-stage form of liver diseases, treatment options for advanced HCC are limited, due to poor liver function. The exosome is a nanometer-sized membrane vesicle structure that originates from the endosome. Exosome-mediated transfer of proteins, DNAs and various forms of RNA, such as microRNA (miRNA), long noncoding RNA (lncRNA) and messenger RNA (mRNA), contributes to the development of HCC. Exosomes mediate communication between both HCC and non-HCC cells involved in tumor-associated cells, and several molecules are implicated in exosome biogenesis. Exosomes may be potential diagnostic biomarkers for early-stage HCC. Exosomal proteins, miRNAs and lncRNAs could provide new biomarker information for HCC. Exosomes are also potential targets for the treatment of HCC. Notably, further efforts are required in this field. We reviewed recent literature and demonstrated how useful exosomes are for diagnosing patients with HCC, treating patients with HCC and predicting the prognosis of HCC patients.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 3
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 23 ( 2021-11-24), p. 12684-
    Abstract: In humans, the coronin family is composed of seven proteins containing WD-repeat domains that regulate actin-based cellular processes. Some members of the coronin family are closely associated with cancer cell migration and invasion. The Cancer Genome Atlas (TCGA) analysis revealed that CORO1C, CORO2A, and CORO7 were significantly upregulated in oral squamous cell carcinoma (OSCC) tissues (p 〈 0.05). Moreover, the high expression of CORO2A was significantly predictive of the 5-year survival rate of patients with OSCC (p = 0.0203). Overexpression of CORO2A was detected in OSCC clinical specimens by immunostaining. siRNA-mediated knockdown of CORO2A suppressed cancer cell migration and invasion abilities. Furthermore, we investigated the involvement of microRNAs (miRNAs) in the molecular mechanism underlying CORO2A overexpression in OSCC cells. TCGA analysis confirmed that tumor-suppressive miR-125b-5p and miR-140-5p were significantly downregulated in OSCC tissues. Notably, these miRNAs bound directly to the 3′-UTR of CORO2A and controlled CORO2A expression in OSCC cells. In summary, we found that aberrant expression of CORO2A facilitates the malignant transformation of OSCC cells, and that downregulation of tumor-suppressive miRNAs is involved in CORO2A overexpression. Elucidation of the interaction between genes and miRNAs will help reveal the molecular pathogenesis of OSCC.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 4
    In: Cells, MDPI AG, Vol. 9, No. 4 ( 2020-04-20), p. 1019-
    Abstract: Malignant pleural mesothelioma (MPM) has extremely limited treatment despite a poor prognosis. Moreover, molecular targeted therapy for MPM has not yet been implemented; thus, a new targeted therapy is highly desirable. Near-infrared photoimmunotherapy (NIR-PIT) is a recently developed cancer therapy that combines the specificity of antibodies for targeting tumors with toxicity induced by the photoabsorber after exposure to NIR-light. In this study, we developed a new phototherapy targeting podoplanin (PDPN) for MPM with the use of both NIR-PIT and an anti-PDPN antibody, NZ-1. An antibody–photosensitizer conjugate consisting of NZ-1 and phthalocyanine dye was synthesized. In vitro NIR-PIT-induced cytotoxicity was measured with both dead cell staining and luciferase activity on various MPM cell lines. In vivo NIR-PIT was examined in both the flank tumor and orthotopic mouse model with in vivo real-time imaging. In vitro NIR-PIT-induced cytotoxicity was NIR-light dose dependent. In vivo NIR-PIT led to significant reduction in both tumor volume and luciferase activity in a flank model (p 〈 0.05, NIR-PIT group versus NZ-1-IR700 group). The PDPN-targeted NIR-PIT resulted in a significant antitumor effect in an MPM orthotopic mouse model (p 〈 0.05, NIR-PIT group versus NZ-1-IR700 group). This study suggests that PDPN-targeted NIR-PIT could be a new promising treatment for MPM.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2661518-6
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  • 5
    In: Genes, MDPI AG, Vol. 14, No. 5 ( 2023-04-27), p. 995-
    Abstract: Coronin proteins are actin-related proteins containing WD repeat domains encoded by seven genes (CORO1A, CORO1B, CORO1C, CORO2A, CORO2B, CORO6, and CORO7) in the human genome. Analysis of large cohort data from The Cancer Genome Atlas revealed that expression of CORO1A, CORO1B, CORO1C, CORO2A, and CORO7 was significantly upregulated in pancreatic ductal adenocarcinoma (PDAC) tissues (p 〈 0.05). Moreover, high expression of CORO1C and CORO2A significantly predicted the 5 year survival rate of patients with PDAC (p = 0.0071 and p = 0.0389, respectively). In this study, we focused on CORO1C and investigated its functional significance and epigenetic regulation in PDAC cells. Knockdown assays using siRNAs targeting CORO1C were performed in PDAC cells. Aggressive cancer cell phenotypes, especially cancer cell migration and invasion, were inhibited by CORO1C knockdown. The involvement of microRNAs (miRNAs) is a molecular mechanism underlying the aberrant expression of cancer-related genes in cancer cells. Our in silico analysis revealed that five miRNAs (miR-26a-5p, miR-29c-3p, miR-130b-5p, miR-148a-5p, and miR-217) are putative candidate miRNAs regulating CORO1C expression in PDAC cells. Importantly, all five miRNAs exhibited tumor-suppressive functions and four miRNAs except miR-130b-5p negatively regulated CORO1C expression in PDAC cells. CORO1C and its downstream signaling molecules are potential therapeutic targets in PDAC.
    Type of Medium: Online Resource
    ISSN: 2073-4425
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2527218-4
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  • 6
    In: Biomedicines, MDPI AG, Vol. 10, No. 3 ( 2022-03-12), p. 663-
    Abstract: Based on our original RNA sequence-based microRNA (miRNA) signatures of head and neck squamous cell carcinoma (HNSCC), it was revealed that the expression levels of miR-1-3p, miR-206, miR-133a-3p, and miR-133b were significantly suppressed in cancer specimens. Seed sequences of miR-1-3p/miR-206 and miR-133a-3p/miR-133b are identical. Interestingly, miR-1-3p/miR-133a-3p and miR-206/miR-133b are clustered in the human genome. We hypothesized that the genes coordinately controlled by these miRNAs are closely involved in the malignant transformation of HNSCC. Our in silico analysis identified a total of 28 genes that had putative miR-1-3p/miR-133a-3p and miR-206/miR-133b binding sites. Moreover, their expression levels were upregulated in HNSCC tissues. Multivariate Cox regression analyses showed that expression of PFN2 and PSEN1 were independent prognostic factors for patients with HNSCC (p 〈 0.05). Notably, four miRNAs (i.e., miR-1-3p, miR-206, miR-133a-3p, and miR-133b) directly bound the 3′untranslated region of PFN2 and controlled expression of the gene in HNSCC cells. Overexpression of PFN2 was confirmed in clinical specimens, and its aberrant expression facilitated cancer cell migration and invasion abilities. Our miRNA-based strategy continues to uncover novel genes closely involved in the oncogenesis of HNSCC.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2720867-9
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  • 7
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 7 ( 2022-03-30), p. 3808-
    Abstract: Recently, our studies revealed that some passenger strands of microRNAs (miRNAs) were closely involved in cancer pathogenesis. Analysis of miRNA expression signatures showed that the expression of miR-30e-3p (the passenger strand of pre-miR-30e) was significantly downregulated in cancer tissues. In this study, we focused on miR-30e-3p (the passenger strand of pre-miR-30e). We addressed target genes controlled by miR-30e-3p that were closely associated with the molecular pathogenesis of head and neck squamous cell carcinoma (HNSCC). Ectopic expression assays demonstrated that the expression of miR-30e-3p attenuated cancer cell malignant phenotypes (e.g., cell proliferation, migration, and invasive abilities). Our analysis of miR-30e-3p targets revealed that 11 genes (ADA, CPNE8, C14orf126, ERGIC2, HMGA2, PLS3, PSMD10, RALB, SERPINE1, SFXN1, and TMEM87B) were expressed at high levels in HNSCC patients. Moreover, they significantly predicted the short survival of HNSCC patients based on 5-year overall survival rates (p 〈 0.05) in The Cancer Genome Atlas (TCGA). Among these targets, SERPINE1 was found to be an independent prognostic factor for patient survival (multivariate Cox regression; hazard ratio = 1.6078, p 〈 0.05). Aberrant expression of SERPINE1 was observed in HNSCC clinical samples by immunohistochemical analysis. Functional assays by targeting SERPINE1 expression revealed that the malignant phenotypes (e.g., proliferation, migration, and invasion abilities) of HNSCC cells were suppressed by the silencing of SERPINE1 expression. Our miRNA-based approach will accelerate our understanding of the molecular pathogenesis of HNSCC.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 8
    In: Biomedicines, MDPI AG, Vol. 8, No. 12 ( 2020-12-12), p. 599-
    Abstract: We previously found that both the guide and passenger strands of the miR-139 duplex (miR-139-5p and miR-139-3p, respectively) were downregulated in cancer tissues. Analysis of TCGA datasets revealed that low expression of miR-139-5p (p 〈 0.0001) and miR-139-3p (p 〈 0.0001) was closely associated with 5-year survival rates of patients with renal cell carcinoma (RCC). Ectopic expression assays showed that miR-139-5p and miR-139-3p acted as tumor-suppressive miRNAs in RCC cells. Here, 19 and 22 genes were identified as putative targets of miR-139-5p and miR-139-3p in RCC cells, respectively. Among these genes, high expression of PLXDC1, TET3, PXN, ARHGEF19, ELK1, DCBLD1, IKBKB, and CSF1 significantly predicted shorter survival in RCC patients according to TCGA analyses (p 〈 0.05). Importantly, the expression levels of four of these genes, PXN, ARHGEF19, ELK1, and IKBKB, were independent prognostic factors for patient survival (p 〈 0.05). We focused on PXN (paxillin) and investigated its potential oncogenic role in RCC cells. PXN knockdown significantly inhibited cancer cell migration and invasion, possibly by regulating epithelial–mesenchymal transition. Involvement of the miR-139-3p passenger strand in RCC molecular pathogenesis is a new concept. Analyses of tumor-suppressive-miRNA-mediated molecular networks provide important insights into the molecular pathogenesis of RCC.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2720867-9
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