Potential for reversing miR-634-mediated cytoprotective processes to improve efficacy of chemotherapy against oral squamous cell carcinoma

Tran, Phuong Xuan; Inoue, Jun; Harada, Hiroyuki; Inazawa, Johji

doi:10.1016/j.omto.2022.02.002

Cited by 5 publications

(6 citation statements)

References 53 publications

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“…Further examination of the target gene and apoptotic marker expression showed downregulated levels of Asct2, Nrf2, and survivin, the corresponding human target genes of miR-634, as well as an increase in apoptotic cell numbers. These results suggested that miR-634 induced apoptosis in CMM cell lines through the same mechanisms that we reported in other human and murine malignant tumor cell lines, including HMM [17][18][19][20][21] This conclusion is crucial because it suggests the compatibility of the miR-634 treatment technique for CMM cases with HMM cases.…”

Section: Discussionsupporting

confidence: 74%

“…We previously demonstrated that the introduction of synthetic double-strand (ds)-miR-634 mimic triggered apoptotic cell death by directly targeting genes associated with cytoprotective processes, including glutaminolysis (ASCT2), autophagy (LAMP2), antioxidant activity (NRF2), anti-apoptotic activity (cIAP1, survivin, APIP, and XIAP), and mitochondrial function (OPA1 and TFAM) in various human cancer cell lines, including those of HMM [17][18][19][20][21]. Delivery of a synthetic ds-miR-634 mimic into tumor cells using lipid nanoparticles (LNPs) as the drug delivery system was therapeutically effective in a xenograft mouse model of pancreatic cancer [19].…”

Section: Introductionmentioning

confidence: 99%

“…Delivery of a synthetic ds-miR-634 mimic into tumor cells using lipid nanoparticles (LNPs) as the drug delivery system was therapeutically effective in a xenograft mouse model of pancreatic cancer [19]. Topical application of an ointment containing ds-miR-634 mimic inhibited in vivo tumor growth without toxicity in a xenograft mouse model of cutaneous and oral squamous cell carcinoma [20,21]. Thus, our previous reports suggested that ds-miR-634 mimic is a useful agent for cancer therapy.…”

Section: Introductionmentioning

confidence: 99%

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Therapeutic applications of local injection of hsa-miR-634 into canine spontaneous malignant melanoma tumors

et al. 2023

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Malignant melanoma (MM) is one of the most common tumors in both dogs and humans. As canine MM (CMM) and human MM (HMM) have similar clinical characteristics, CMM appears to be a good clinical model for HMM. We previously demonstrated that the introduction of a synthetic double-strand-microRNA-634 (miR-634) mimic triggered apoptotic cell death by directly targeting the genes associated with cytoprotective processes in various human cancer cell lines, including those of HMM. This study aimed to investigate the antitumor effects of topical administration of miR-634 on spontaneous CMMs to provide a basis for future applications of miR-634 formulations in HMM treatment. We found that miR-634 administration induced apoptosis in CMM cell lines in vitro via downregulation of Asct2, Nrf2, and survivin expression, similar to the mechanisms in HMM cell lines. Furthermore, intratumoral miR-634 administration induced antitumor effects in four of seven spontaneous CMM cases, with no adverse effects. Local administration of miR-634 to lung metastasis under ultrasound guidance induced tumor shrinkage. These results con rm the antitumor effect of topical administration of miR-634 in spontaneous CMM, a model for spontaneous HMM, thereby providing a novel treatment strategy for HMM.

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Section: Discussionsupporting

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Therapeutic applications of local injection of hsa-miR-634 into canine spontaneous malignant melanoma tumors

et al. 2023

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“…Apaf-1 interacting protein (APIP) functions as an endogenous inhibitor of apoptotic cell death by inhibiting caspase activity. Its upregulation leads to chemotherapeutic resistance in cancer cells [ 75 ]. In our work, we did not find changes in APIP level in HNSCC patients, but it can be assumed that evaluation of the expression level of this gene will be of interest to researchers when studying the mechanisms of tumor therapeutic resistance.…”

Section: Discussionmentioning

confidence: 99%

Gene-Expression Patterns of Tumor and Peritumor Tissues of Smoking and Non-Smoking HPV-Negative Patients with Head and Neck Squamous Cell Carcinoma

Soboleva,

Arutyunyan,

Jumaniyazova

et al. 2024

Biomedicines

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We studied the gene-expression patterns in specimens of tumor and peritumor tissue biopsies of 26 patients with head and neck carcinomas depending on smoking status. Histological and immunohistochemical examinations verified that all tumors belonged to the “classical” subgroup of head and neck carcinomas, and the HPV-negative tumor status was confirmed. The expression of 28 tumor-associated genes determined by RT-PCR was independent of patients’ sex or age, TNM status, degree of differentiation, or tissue localization. Moreover, in peritumor tissue, none of the 28 genes were differentially expressed between the groups of smoking and nonsmoking patients. During oncotransformation in both studied groups, there were similar processes typical for HNSCC progression: the expression levels of paired keratins 4 and 13 were reduced, while the expression levels of keratin 17 and CD44 were significantly increased. However, further investigation revealed some distinctive features: the expression of the genes EGFR and TP63 increased significantly only in the nonsmoking group, and the expression of IL6, CDKN2A, EGF, and PITX1 genes changed only in the smoking group. In addition, correlation analysis identified several clusters within which genes displayed correlations in their expression levels. The largest group included 10 genes: TIMP1, TIMP2, WEE1, YAP, HIF1A, PI3KCA, UTP14A, APIP, PTEN, and SLC26A6. The genetic signatures associated with smoking habits that we have found may serve as a prerequisite for the development of diagnostic panels/tests predicting responses to different therapeutic strategies for HNSCC.

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“…10,11 Research on nucleic acid therapeutics using miRNAs against cancer are no more at a level of infancy; such therapeutics are undergoing phase I and II testing in humans. [12][13][14][15] Some organ-specific miRNAs regulate PKM isoform expression by directly targeting PTBP1, which is the splicer responsible for PKM2-dominant expression. 16 The miRNAs targeting PTBP1 are extensively studied because of their role in regulating cancer-specific energy metabolism (ie, the Warburg effect).…”

Section: Introductionmentioning

confidence: 99%

Experimental Study of Warburg Effect in Keloid Nodules: Implication for Downregulation of miR-133b

Lee

Ito

Taniguchi

et al. 2023

Plastic and Reconstructive Surgery - Global Open

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Background: A keloid is composed of several nodules, which are divided into two zones: the central zone (CZ; a hypoxic region) and the marginal zone (MZ; a normoxic region). Keloid nodules play a key role in energy metabolic activity for continuous growth by increasing in number and total area. In this study, we aimed to investigate the roles of the zones in the execution of the Warburg effect and identify which microRNAs regulate this phenomenon in keloid tissue. Methods: Eleven keloids from patients were used. Using immunohistochemical analysis, 179 nodules were randomly chosen from these keloids to identify glycolytic enzymes, autophagic markers, pyruvate kinase M (PKM) 1/2, and polypyrimidine tract binding protein 1 (PTBP1). Western blot and qRT-PCR tests were also performed for PKM, PTBP1, and microRNAs (miR-133b and miR-200b, c). Results: Immunohistochemical analysis showed that the expression of the autophagic (LC3, p62) and glycolytic (GLUT1, HK2) were significantly higher in the CZ than in the MZ. PKM2 expression was significantly higher than PKM1 expression in keloid nodules. Furthermore, PKM2 expression was higher in the CZ than in the MZ. However, PKM1 and PTBP1 expression levels were higher in the MZ than in the CZ. The qRT-PCR analysis showed that miR-133b-3p was moderately downregulated in the keloids compared with its expression in the normal skin tissue. Conclusions: The Warburg effect occurred individually in nodules. The MZ presented PKM2-positive fibroblasts produced by activated PTBP1. In the CZ, PKM2-positive fibroblasts produced lactate. MiR-133b-3p was predicted to control the Warburg effect in keloids.

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Potential for reversing miR-634-mediated cytoprotective processes to improve efficacy of chemotherapy against oral squamous cell carcinoma

Cited by 5 publications

References 53 publications

Therapeutic applications of local injection of hsa-miR-634 into canine spontaneous malignant melanoma tumors

Therapeutic applications of local injection of hsa-miR-634 into canine spontaneous malignant melanoma tumors

Gene-Expression Patterns of Tumor and Peritumor Tissues of Smoking and Non-Smoking HPV-Negative Patients with Head and Neck Squamous Cell Carcinoma

Experimental Study of Warburg Effect in Keloid Nodules: Implication for Downregulation of miR-133b

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