Keigo Miura - Academia.edu (original) (raw)

Papers by Keigo Miura

Research paper thumbnail of Conversion of Human Hepatoma Cells by 520d-5p to Benign or Normal Liver Tissues via a stemness-Mediated Process

Oncogen, 2020

The human ncRNA gene RGM249 regulates the extent of differentiation of cancer cells and the conve... more The human ncRNA gene RGM249 regulates the extent of differentiation of cancer cells and the conversion of 293FT cells to hiPSCs. To identify the factors underlying this process, we investigated the effects of lentivirally inducing miR-520d expression in 293FT and HLF cells in vitro. Subsequently, we evaluated tumor formation in a xenograft model. Transformed HLF cells were Oct4 and Nanog positive within 24 h, showed p53 upregulation and hTERT downregulation, and mostly lost their migration abilities. After lentiviral infection, the cells were intraperitoneally injected into mice, resulting in benign teratomas (6%), the absence of tumors (87%) or differentiation into benign liver tissues (7%) at the injection site after one month. We are the first to demonstrate the loss of malignant properties in cancer cells in vivo through the expression of a single microRNA (miRNA). This miRNA successfully converted 293FT and hepatoma cells to hiPSC-like cells. The regulation of malignancy by miR-520dappears to be through the conversion of cancer cells to normal stem cells.

Research paper thumbnail of Additional file 4: Table S3. of Tumor-suppressive effects of atelocollagen-conjugated hsa-miR-520d-5p on un-differentiated cancer cells in a mouse xenograft model

Effective rate of tumor disappearance. Effective rate (%) of tumor disappearance by systemic admi... more Effective rate of tumor disappearance. Effective rate (%) of tumor disappearance by systemic administration compared with that of the control is shown in Table 1. Greater than 75 % of the tumor cells disappeared based on macroscopic and microscopic observation. (PDF 94 kb)

Research paper thumbnail of Additional file 5: Figure S6. of Tumor-suppressive effects of atelocollagen-conjugated hsa-miR-520d-5p on un-differentiated cancer cells in a mouse xenograft model

Representative gene expression in HMV-I tumors without suppression. When the animals were sacrifi... more Representative gene expression in HMV-I tumors without suppression. When the animals were sacrificed, most tumors grew increasingly and the suppressive effect of 520d-5p on tumor growth could not be observed by RT-PCR. *: Pâ

Research paper thumbnail of Additional file 1: Table S1. of Tumor-suppressive effects of atelocollagen-conjugated hsa-miR-520d-5p on un-differentiated cancer cells in a mouse xenograft model

The sequences of primers used in this study. Primers used in this study are presented. (PDF 69 kb)

Research paper thumbnail of Additional file 2: Figure S5. of Tumor-suppressive effects of atelocollagen-conjugated hsa-miR-520d-5p on un-differentiated cancer cells in a mouse xenograft model

A representative case 24Â weeks after subcutaneous injection. A pathologist recognized adipose ti... more A representative case 24Â weeks after subcutaneous injection. A pathologist recognized adipose tissue and skeletal muscle thought to be the existing structure but could not confirm the clear tumor composition at the injection site (HE stain; top left, the perspective of the specimen; bottom, x40, x100 magnification). We did not identify any macroscopic tumors in this case. (PDF 341 kb)

Research paper thumbnail of Additional file 8: Figure S3. of Tumor-suppressive effects of atelocollagen-conjugated hsa-miR-520d-5p on un-differentiated cancer cells in a mouse xenograft model

An in vivo study using glioblastoma cells (T98G) treated with miR-520d-5p (520d/T98G). Three surv... more An in vivo study using glioblastoma cells (T98G) treated with miR-520d-5p (520d/T98G). Three surviving mice were examined for human-derived gene expression in murine brain tissue 3 months after intracranial injection. a KSN/Slc mice were anesthetized with sodium pentobarbital (50 mg/kg intraperitoneally) and placed in a stereotaxic apparatus. During surgery, the animals' body temperature was maintained at 37 °C using a heating pad. The skull was exposed, and a small craniotomy was made over the left striatum. A 30-gauge injection needle connected to a 10-μl Hamilton syringe through polyethylene tubing was used for 520d/T98G cell transplantation. The injection needle was inserted stereotaxically into the left striatum (A 2.0 mm, L 0.5 mm, D 1.2 mm from bregma) (left), and 1 μl of cell suspension (1 × 108 cells/μl) was pressure-injected (right). After injection, the needle was slowly withdrawn, and the skull hole was covered with dental cement. The incision was sutured with 6-0 Pr...

Research paper thumbnail of Additional file 7: Figure S2. of Tumor-suppressive effects of atelocollagen-conjugated hsa-miR-520d-5p on un-differentiated cancer cells in a mouse xenograft model

The side effects of 520d/atelocollagen and the presence of tumor cells in the inoculated tumor in... more The side effects of 520d/atelocollagen and the presence of tumor cells in the inoculated tumor in seven organs. Neither the presence of embolism induced by atelocollagen or evidence of micrometastases was detected pathologically in brain, liver, spleen, heart, lung, small intestine and kidney. (PDF 185 kb)

Research paper thumbnail of Additional file 3: Table S2. of Tumor-suppressive effects of atelocollagen-conjugated hsa-miR-520d-5p on un-differentiated cancer cells in a mouse xenograft model

The suppression rate (%) of tumor volume. The suppression rate (%) of tumor volume compared with ... more The suppression rate (%) of tumor volume. The suppression rate (%) of tumor volume compared with the control each week is shown in Table 1. Greater than 85 % suppression 6 weeks after administration was observed in a xenograft model by subcutaneous injection. (PDF 92 kb)

Research paper thumbnail of Additional file 9: Table S4. of Tumor-suppressive effects of atelocollagen-conjugated hsa-miR-520d-5p on un-differentiated cancer cells in a mouse xenograft model

Subcutaneous changes of 520d-5p-expressing HMV-I in a xenograft model. Subcutaneous changes of 52... more Subcutaneous changes of 520d-5p-expressing HMV-I in a xenograft model. Subcutaneous changes of 520d-5p-expressing HMV-I in a xenograft model were recorded as criteria for tumor formation and metastasis. In HMV-I, the disappearance rate of tumors was greater than the outcome (12.5Â %) of therapeutic administration in vivo. (PDF 32 kb)

Research paper thumbnail of Additional file 10: Figure S4. of Tumor-suppressive effects of atelocollagen-conjugated hsa-miR-520d-5p on un-differentiated cancer cells in a mouse xenograft model

Relative mRNA expression levels of BRAF, PDCD1 and PDCD1LG2, standardized to β-actin in HMV-I cel... more Relative mRNA expression levels of BRAF, PDCD1 and PDCD1LG2, standardized to β-actin in HMV-I cells. A box plot was drawn to compare expression levels. BRAF was not significantly downregulated in 520d/HMV-I cells compared with mock/HMV-I cells (by Mann-Whitney U test, n = 3), but it tended to be downregulated by 520d-5p. *, P

Research paper thumbnail of Additional file 2: of miR-520d-5p can reduce the mutations in hepatoma cancer cells and iPSCs-derivatives

Summary of nucleotides alterations in respective genes regarding of our interest (Tables S1â S7).... more Summary of nucleotides alterations in respective genes regarding of our interest (Tables S1â S7). (DOCX 26 kb)

Research paper thumbnail of Additional file 1: of miR-520d-5p can reduce the mutations in hepatoma cancer cells and iPSCs-derivatives

Figure S1. Representative conversion in Kat8 after 520d-5p transfection. Figure S2. Comparative N... more Figure S1. Representative conversion in Kat8 after 520d-5p transfection. Figure S2. Comparative NGS analysis between hiPSC, 520d/hMSC progenitor cells, or hMSC. Figure S3. Comparative NGS analysis between hiPSC, 520d/hMSC progenitor cells, or hMSC regarding representative DNA repair genes. Figure S4. PCR array using RT2 Profiler PCR array system regarding epigenetics-related genes in 520d/HLF (5D, 7D) and hiPSC. (PDF 835 kb)

Research paper thumbnail of miR-520d-5p can reduce the mutations in hepatoma cancer cells and iPSCs-derivatives

BMC Cancer, 2019

Background: Human microRNAs (miRNAs) have diverse functions in biology, and play a role in nearly... more Background: Human microRNAs (miRNAs) have diverse functions in biology, and play a role in nearly every biological process. Here we report that miR-520d-5p (520d-5p) causes undifferentiated cancer cells to adopt benign or normal status in vivo in immunodeficient mice via demethylation and P53 upregulation. Further we found that 520-5p causes normal cells to elongate cellular lifetime and mesenchymal stem cell-like status with CD105 positivity. We hypothesized that ectopic 520d-5p expression reduced mutations in undifferentiated type of hepatoma (HLF) cells through synergistic modulation of methylation-related enzymatic expression. Methods: To examine whether there were any changes in mutation status in cells treated with 520d-5p, we performed next generation sequencing (NGS) in HLF cells and human iPSC-derivative cells in pre-mesenchymal stem cell status. We analyzed the data using both genome-wide and individual gene function approaches. Results: 520d-5p induced a shift towards a wild type or non-malignant phenotype, which was regulated by nucleotide mutations in both HLF cells and iPSCs. Further, 520d-5p reduced mutation levels in both the whole genome and genomic fragment assemblies. Conclusions: Cancer cell genomic mutations cannot be repaired in most contexts. However, these findings suggest that applied development of 520d-5p would allow new approaches to cancer research and improve the quality of iPSCs used in regenerative medicine.

Research paper thumbnail of Correction to: Tumor-suppressive effects of atelocollagen-conjugated hsa-miR-520d-5p on un-differentiated cancer cells in a mouse xenograft model

Research paper thumbnail of Hsa-miR-520d-5p promotes survival in human dermal fibroblasts exposed to a lethal dose of UV irradiation

npj Aging and Mechanisms of Disease, 2016

We previously reported that hsa-miR-520d-5p is functionally involved in the induction of the epit... more We previously reported that hsa-miR-520d-5p is functionally involved in the induction of the epithelial-mesenchymal transition and stemness-mediated processes in normal cells and cancer cells, respectively. On the basis of the synergistic effect of p53 upregulation and demethylation induced by 520d-5p, the current study investigated the effect of this miRNA on apoptotic induction by ultraviolet B (UVB) light in normal human dermal fibroblast (NHDF) cells. 520d-5p was lentivirally transfected into NHDF cells either before or after a lethal dose of UVB irradiation (302 nm) to assess its preventive or therapeutic effects, respectively. The methylation level, gene expression, production of type I collagen and cell cycle distribution were estimated in UV-irradiated cells. NHDF cells transfected with 520d-5p prior to UVB irradiation had apoptotic characteristics, and the transfection exerted no preventive effects. However, transfection with 520d-5p into NHDF cells after UVB exposure resulted in the induction of reprogramming in damaged fibroblasts, the survival of CD105-positive cells, an extended cell lifespan and prevention of cellular damage or malfunction; these outcomes were similar to the effects observed in 520d-5p-transfected NHDF cells (520d/NHDF). The gene expression of c-Abl (Abelson murine leukemia viral oncogene homolog 1), ATR (ataxia telangiectasia and Rad3-related protein), and BRCA1 (breast cancer susceptibility gene I) in transfectants was transcriptionally upregulated in order. These mechanistic findings indicate that ATR-dependent DNA damage repair was activated under this stressor. In conclusion, 520d-5p exerted a therapeutic effect on cells damaged by UVB and restored them to a normal senescent state following functional restoration via survival of CD105-positive cells through c-Abl-ATR-BRCA1 pathway activation, p53 upregulation, and demethylation.

Research paper thumbnail of Tumor-suppressive effects of atelocollagen-conjugated hsa-miR-520d-5p on un-differentiated cancer cells in a mouse xenograft model

BMC cancer, Jul 7, 2016

We previously demonstrated that hsa-miR-520d-5p can convert cancer cells into induced pluripotent... more We previously demonstrated that hsa-miR-520d-5p can convert cancer cells into induced pluripotent stem cells (iPSCs) or mesenchymal stem cells (MSCs) via a demethylation process and p53 upregulation in vivo. Additionally, we have reported the non-tumorigenic effect of miR-520d-5p on normal human cells, including fibroblasts. We used atelocollagen-conjugated miR-520d-5p (520d/atelocollagen) to confirm the possibility of a therapeutic effect on cancer cells. We traced the size and signal intensity of GFP-expressing tumors in mice each week, beginning 4 weeks after subcutaneous inoculation. 520d/atelocollagen treatment suppressed tumor growth by greater than 80 % each week relative to controls and resulted in an approximately 30 % disappearance of tumors. In mice whose tumors disappeared, the existence of human genomic material at the injection site was examined by quantitative Alu-PCR, and we confirmed the co-existence of both species-derived cells. In every site where a tumor disappe...

Research paper thumbnail of A novel anti-cancer effect of atelocollagen-conjugated miR-520d-5p on pancreatic cancer cells in vitro and in a mouse xenograft model

Integrative Molecular Medicine, 2019

Research paper thumbnail of Comparative study of (18) F-FDG-PET/CT imaging and serum hTERT mRNA quantification in cancer diagnosis

Cancer medicine, Jan 15, 2015

We have reported on the clinical usefulness of human telomerase reverse transcriptase (hTERT) mRN... more We have reported on the clinical usefulness of human telomerase reverse transcriptase (hTERT) mRNA quantification in sera in patients with several cancers. Positron emission tomography-computed tomography (PET/CT) using (18) F-fluorodeoxyglucose (FDG) has recently become an excellent modality for detecting cancer. We performed a diagnostic comparative study of FDG-PET/CT and hTERT mRNA quantification in patients with cancer. Four hundred seventy subjects, including 125 healthy individuals and 345 outpatients with cancer who had received medical treatments for cancer in their own or other hospitals, were enrolled. The subjects were diagnosed by FDG-PET/CT, and we measured their serum hTERT mRNA levels using real-time RT-PCR, correlating the quantified values with the clinical course. In this prospective study, we statistically assessed the sensitivity and specificity, and their clinical significance. hTERT mRNA and FDG-PET/CT were demonstrated to be correlated with the clinical param...

Research paper thumbnail of Conversion of Human Hepatoma Cells by 520d-5p to Benign or Normal Liver Tissues via a stemness-Mediated Process

Oncogen, 2020

The human ncRNA gene RGM249 regulates the extent of differentiation of cancer cells and the conve... more The human ncRNA gene RGM249 regulates the extent of differentiation of cancer cells and the conversion of 293FT cells to hiPSCs. To identify the factors underlying this process, we investigated the effects of lentivirally inducing miR-520d expression in 293FT and HLF cells in vitro. Subsequently, we evaluated tumor formation in a xenograft model. Transformed HLF cells were Oct4 and Nanog positive within 24 h, showed p53 upregulation and hTERT downregulation, and mostly lost their migration abilities. After lentiviral infection, the cells were intraperitoneally injected into mice, resulting in benign teratomas (6%), the absence of tumors (87%) or differentiation into benign liver tissues (7%) at the injection site after one month. We are the first to demonstrate the loss of malignant properties in cancer cells in vivo through the expression of a single microRNA (miRNA). This miRNA successfully converted 293FT and hepatoma cells to hiPSC-like cells. The regulation of malignancy by miR-520dappears to be through the conversion of cancer cells to normal stem cells.

Research paper thumbnail of Additional file 4: Table S3. of Tumor-suppressive effects of atelocollagen-conjugated hsa-miR-520d-5p on un-differentiated cancer cells in a mouse xenograft model

Effective rate of tumor disappearance. Effective rate (%) of tumor disappearance by systemic admi... more Effective rate of tumor disappearance. Effective rate (%) of tumor disappearance by systemic administration compared with that of the control is shown in Table 1. Greater than 75 % of the tumor cells disappeared based on macroscopic and microscopic observation. (PDF 94 kb)

Research paper thumbnail of Additional file 5: Figure S6. of Tumor-suppressive effects of atelocollagen-conjugated hsa-miR-520d-5p on un-differentiated cancer cells in a mouse xenograft model

Representative gene expression in HMV-I tumors without suppression. When the animals were sacrifi... more Representative gene expression in HMV-I tumors without suppression. When the animals were sacrificed, most tumors grew increasingly and the suppressive effect of 520d-5p on tumor growth could not be observed by RT-PCR. *: Pâ

Research paper thumbnail of Additional file 1: Table S1. of Tumor-suppressive effects of atelocollagen-conjugated hsa-miR-520d-5p on un-differentiated cancer cells in a mouse xenograft model

The sequences of primers used in this study. Primers used in this study are presented. (PDF 69 kb)

Research paper thumbnail of Additional file 2: Figure S5. of Tumor-suppressive effects of atelocollagen-conjugated hsa-miR-520d-5p on un-differentiated cancer cells in a mouse xenograft model

A representative case 24Â weeks after subcutaneous injection. A pathologist recognized adipose ti... more A representative case 24Â weeks after subcutaneous injection. A pathologist recognized adipose tissue and skeletal muscle thought to be the existing structure but could not confirm the clear tumor composition at the injection site (HE stain; top left, the perspective of the specimen; bottom, x40, x100 magnification). We did not identify any macroscopic tumors in this case. (PDF 341 kb)

Research paper thumbnail of Additional file 8: Figure S3. of Tumor-suppressive effects of atelocollagen-conjugated hsa-miR-520d-5p on un-differentiated cancer cells in a mouse xenograft model

An in vivo study using glioblastoma cells (T98G) treated with miR-520d-5p (520d/T98G). Three surv... more An in vivo study using glioblastoma cells (T98G) treated with miR-520d-5p (520d/T98G). Three surviving mice were examined for human-derived gene expression in murine brain tissue 3 months after intracranial injection. a KSN/Slc mice were anesthetized with sodium pentobarbital (50 mg/kg intraperitoneally) and placed in a stereotaxic apparatus. During surgery, the animals' body temperature was maintained at 37 °C using a heating pad. The skull was exposed, and a small craniotomy was made over the left striatum. A 30-gauge injection needle connected to a 10-μl Hamilton syringe through polyethylene tubing was used for 520d/T98G cell transplantation. The injection needle was inserted stereotaxically into the left striatum (A 2.0 mm, L 0.5 mm, D 1.2 mm from bregma) (left), and 1 μl of cell suspension (1 × 108 cells/μl) was pressure-injected (right). After injection, the needle was slowly withdrawn, and the skull hole was covered with dental cement. The incision was sutured with 6-0 Pr...

Research paper thumbnail of Additional file 7: Figure S2. of Tumor-suppressive effects of atelocollagen-conjugated hsa-miR-520d-5p on un-differentiated cancer cells in a mouse xenograft model

The side effects of 520d/atelocollagen and the presence of tumor cells in the inoculated tumor in... more The side effects of 520d/atelocollagen and the presence of tumor cells in the inoculated tumor in seven organs. Neither the presence of embolism induced by atelocollagen or evidence of micrometastases was detected pathologically in brain, liver, spleen, heart, lung, small intestine and kidney. (PDF 185 kb)

Research paper thumbnail of Additional file 3: Table S2. of Tumor-suppressive effects of atelocollagen-conjugated hsa-miR-520d-5p on un-differentiated cancer cells in a mouse xenograft model

The suppression rate (%) of tumor volume. The suppression rate (%) of tumor volume compared with ... more The suppression rate (%) of tumor volume. The suppression rate (%) of tumor volume compared with the control each week is shown in Table 1. Greater than 85 % suppression 6 weeks after administration was observed in a xenograft model by subcutaneous injection. (PDF 92 kb)

Research paper thumbnail of Additional file 9: Table S4. of Tumor-suppressive effects of atelocollagen-conjugated hsa-miR-520d-5p on un-differentiated cancer cells in a mouse xenograft model

Subcutaneous changes of 520d-5p-expressing HMV-I in a xenograft model. Subcutaneous changes of 52... more Subcutaneous changes of 520d-5p-expressing HMV-I in a xenograft model. Subcutaneous changes of 520d-5p-expressing HMV-I in a xenograft model were recorded as criteria for tumor formation and metastasis. In HMV-I, the disappearance rate of tumors was greater than the outcome (12.5Â %) of therapeutic administration in vivo. (PDF 32 kb)

Research paper thumbnail of Additional file 10: Figure S4. of Tumor-suppressive effects of atelocollagen-conjugated hsa-miR-520d-5p on un-differentiated cancer cells in a mouse xenograft model

Relative mRNA expression levels of BRAF, PDCD1 and PDCD1LG2, standardized to β-actin in HMV-I cel... more Relative mRNA expression levels of BRAF, PDCD1 and PDCD1LG2, standardized to β-actin in HMV-I cells. A box plot was drawn to compare expression levels. BRAF was not significantly downregulated in 520d/HMV-I cells compared with mock/HMV-I cells (by Mann-Whitney U test, n = 3), but it tended to be downregulated by 520d-5p. *, P

Research paper thumbnail of Additional file 2: of miR-520d-5p can reduce the mutations in hepatoma cancer cells and iPSCs-derivatives

Summary of nucleotides alterations in respective genes regarding of our interest (Tables S1â S7).... more Summary of nucleotides alterations in respective genes regarding of our interest (Tables S1â S7). (DOCX 26 kb)

Research paper thumbnail of Additional file 1: of miR-520d-5p can reduce the mutations in hepatoma cancer cells and iPSCs-derivatives

Figure S1. Representative conversion in Kat8 after 520d-5p transfection. Figure S2. Comparative N... more Figure S1. Representative conversion in Kat8 after 520d-5p transfection. Figure S2. Comparative NGS analysis between hiPSC, 520d/hMSC progenitor cells, or hMSC. Figure S3. Comparative NGS analysis between hiPSC, 520d/hMSC progenitor cells, or hMSC regarding representative DNA repair genes. Figure S4. PCR array using RT2 Profiler PCR array system regarding epigenetics-related genes in 520d/HLF (5D, 7D) and hiPSC. (PDF 835 kb)

Research paper thumbnail of miR-520d-5p can reduce the mutations in hepatoma cancer cells and iPSCs-derivatives

BMC Cancer, 2019

Background: Human microRNAs (miRNAs) have diverse functions in biology, and play a role in nearly... more Background: Human microRNAs (miRNAs) have diverse functions in biology, and play a role in nearly every biological process. Here we report that miR-520d-5p (520d-5p) causes undifferentiated cancer cells to adopt benign or normal status in vivo in immunodeficient mice via demethylation and P53 upregulation. Further we found that 520-5p causes normal cells to elongate cellular lifetime and mesenchymal stem cell-like status with CD105 positivity. We hypothesized that ectopic 520d-5p expression reduced mutations in undifferentiated type of hepatoma (HLF) cells through synergistic modulation of methylation-related enzymatic expression. Methods: To examine whether there were any changes in mutation status in cells treated with 520d-5p, we performed next generation sequencing (NGS) in HLF cells and human iPSC-derivative cells in pre-mesenchymal stem cell status. We analyzed the data using both genome-wide and individual gene function approaches. Results: 520d-5p induced a shift towards a wild type or non-malignant phenotype, which was regulated by nucleotide mutations in both HLF cells and iPSCs. Further, 520d-5p reduced mutation levels in both the whole genome and genomic fragment assemblies. Conclusions: Cancer cell genomic mutations cannot be repaired in most contexts. However, these findings suggest that applied development of 520d-5p would allow new approaches to cancer research and improve the quality of iPSCs used in regenerative medicine.

Research paper thumbnail of Correction to: Tumor-suppressive effects of atelocollagen-conjugated hsa-miR-520d-5p on un-differentiated cancer cells in a mouse xenograft model

Research paper thumbnail of Hsa-miR-520d-5p promotes survival in human dermal fibroblasts exposed to a lethal dose of UV irradiation

npj Aging and Mechanisms of Disease, 2016

We previously reported that hsa-miR-520d-5p is functionally involved in the induction of the epit... more We previously reported that hsa-miR-520d-5p is functionally involved in the induction of the epithelial-mesenchymal transition and stemness-mediated processes in normal cells and cancer cells, respectively. On the basis of the synergistic effect of p53 upregulation and demethylation induced by 520d-5p, the current study investigated the effect of this miRNA on apoptotic induction by ultraviolet B (UVB) light in normal human dermal fibroblast (NHDF) cells. 520d-5p was lentivirally transfected into NHDF cells either before or after a lethal dose of UVB irradiation (302 nm) to assess its preventive or therapeutic effects, respectively. The methylation level, gene expression, production of type I collagen and cell cycle distribution were estimated in UV-irradiated cells. NHDF cells transfected with 520d-5p prior to UVB irradiation had apoptotic characteristics, and the transfection exerted no preventive effects. However, transfection with 520d-5p into NHDF cells after UVB exposure resulted in the induction of reprogramming in damaged fibroblasts, the survival of CD105-positive cells, an extended cell lifespan and prevention of cellular damage or malfunction; these outcomes were similar to the effects observed in 520d-5p-transfected NHDF cells (520d/NHDF). The gene expression of c-Abl (Abelson murine leukemia viral oncogene homolog 1), ATR (ataxia telangiectasia and Rad3-related protein), and BRCA1 (breast cancer susceptibility gene I) in transfectants was transcriptionally upregulated in order. These mechanistic findings indicate that ATR-dependent DNA damage repair was activated under this stressor. In conclusion, 520d-5p exerted a therapeutic effect on cells damaged by UVB and restored them to a normal senescent state following functional restoration via survival of CD105-positive cells through c-Abl-ATR-BRCA1 pathway activation, p53 upregulation, and demethylation.

Research paper thumbnail of Tumor-suppressive effects of atelocollagen-conjugated hsa-miR-520d-5p on un-differentiated cancer cells in a mouse xenograft model

BMC cancer, Jul 7, 2016

We previously demonstrated that hsa-miR-520d-5p can convert cancer cells into induced pluripotent... more We previously demonstrated that hsa-miR-520d-5p can convert cancer cells into induced pluripotent stem cells (iPSCs) or mesenchymal stem cells (MSCs) via a demethylation process and p53 upregulation in vivo. Additionally, we have reported the non-tumorigenic effect of miR-520d-5p on normal human cells, including fibroblasts. We used atelocollagen-conjugated miR-520d-5p (520d/atelocollagen) to confirm the possibility of a therapeutic effect on cancer cells. We traced the size and signal intensity of GFP-expressing tumors in mice each week, beginning 4 weeks after subcutaneous inoculation. 520d/atelocollagen treatment suppressed tumor growth by greater than 80 % each week relative to controls and resulted in an approximately 30 % disappearance of tumors. In mice whose tumors disappeared, the existence of human genomic material at the injection site was examined by quantitative Alu-PCR, and we confirmed the co-existence of both species-derived cells. In every site where a tumor disappe...

Research paper thumbnail of A novel anti-cancer effect of atelocollagen-conjugated miR-520d-5p on pancreatic cancer cells in vitro and in a mouse xenograft model

Integrative Molecular Medicine, 2019

Research paper thumbnail of Comparative study of (18) F-FDG-PET/CT imaging and serum hTERT mRNA quantification in cancer diagnosis

Cancer medicine, Jan 15, 2015

We have reported on the clinical usefulness of human telomerase reverse transcriptase (hTERT) mRN... more We have reported on the clinical usefulness of human telomerase reverse transcriptase (hTERT) mRNA quantification in sera in patients with several cancers. Positron emission tomography-computed tomography (PET/CT) using (18) F-fluorodeoxyglucose (FDG) has recently become an excellent modality for detecting cancer. We performed a diagnostic comparative study of FDG-PET/CT and hTERT mRNA quantification in patients with cancer. Four hundred seventy subjects, including 125 healthy individuals and 345 outpatients with cancer who had received medical treatments for cancer in their own or other hospitals, were enrolled. The subjects were diagnosed by FDG-PET/CT, and we measured their serum hTERT mRNA levels using real-time RT-PCR, correlating the quantified values with the clinical course. In this prospective study, we statistically assessed the sensitivity and specificity, and their clinical significance. hTERT mRNA and FDG-PET/CT were demonstrated to be correlated with the clinical param...