• Oncology Letters
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• 제17권5호
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• pp.4726-4734
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• 2019

Colorectal cancer (CRC) is one of the most common types of cancers, as evidenced by the >1.2 million patient diagnoses and 600,000 mortalities globally each year. Recently, the microRNA (miR/miRNA)-34 miRNA precursor family was revealed to participate in the tumor protein (TP)-53 pathway, which is frequently involved in CRC. Furthermore, the expression of miR-34 is reportedly regulated by DNA methylation. Accordingly, the present study investigated the correlation between the methylation status of miR-34 miRNAs and miR-34 expression in paired CRC tumor and normal tissues. The methylation status of miR-34a and miR-34b/c was determined using the MethyLight assay, and the expression of miR-34a and miR-34b/c in the same paired tissues was analyzed by reverse transcription-quantitative polymerase chain reaction. The results revealed significantly elevated miR-34a (P=0.012) and miR-34b/c (P<0.0001) methylation levels in tumor tissues when compared with normal tissues, whereas only the expression of miR-34b/c differed (P=0.005) between the paired tissues. In addition, an association between TP53 haplotypes and miR-34 family expression levels was observed. The miR-34a methylation levels in the TP53 PIN A1A1 (48.56±36.49) and TP53 MSP GG (49.00±36.44) genotypes were increased in the tumor tissues when compared with normal tissues. In conclusion, it was determined that miR-34 promoter methylation and TP53 polymorphisms may be associated with CRC pathogenesis.

• Molecules and Cells
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• 제45권6호
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• pp.403-412
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• 2022

Hypoxia leads to significant cellular stress that has diverse pathological consequences such as cardiovascular diseases and cancers. MicroRNAs (miRNAs) are one of regulators of the adaptive pathway in hypoxia. We identified a hypoxia-induced miRNA, miR-34c, that was significantly upregulated in hypoxic human umbilical cord vein endothelial cells (HUVECs) and in murine blood vessels on day 3 of hindlimb ischemia (HLI). miR-34c directly inhibited BCL2 expression, acting as a toggle switch between apoptosis and autophagy in vitro and in vivo. BCL2 repression by miR-34c activated autophagy, which was evaluated by the expression of LC3-II. Overexpression of miR-34c inhibited apoptosis in HUVEC as well as in a murine model of HLI, and increased cell viability in HUVEC. Importantly, the number of viable cells in the blood vessels following HLI was increased by miR-34c overexpression. Collectively, our findings show that miR-34c plays a protective role in hypoxia, suggesting a novel therapeutic target for hypoxic and ischemic diseases in the blood vessels.

• Asian-Australasian Journal of Animal Sciences
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• 제28권11호
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• pp.1532-1536
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• 2015

To verified the target genes of miR-34c, bioinformatics software was used to predict the targets of miR-34c. Three possible target genes of miR-34c related to spermatogenesis and male reproductive development: zinc finger protein 148 (ZNF148), kruppel-like factor 4 (KLF4), and platelet-derived growth factor receptor alpha (PDGFRA) were predicted. Then, the expression of miR-34c and its target genes were detected in swine testicular tissue at different developmental stages by quantitative polymerase chain reaction. The results suggested that the expression of PDGFRA has the highest negative correlation with miR-34c. Then immunohistochemical staining was done to observe the morphology of swine testicular tissue at 2-days and 3, 4, 5-months of age, which indicated that PDGFRA was mainly expressed in the support cells near the basement membrane during the early development stages of testicular tissue, but that the expression of PDGFRA was gradually reduced in later stages. Therefore, western blot analyzed that the highest expression of PDGFRA was generated in 2-days old testicular tissues and the expression levels reduced at 3 and 4-months old, which correlated with the results of immunohistochemical staining. In conclusion, PDGFRA is a target gene of miR-34c.

• Asian Pacific Journal of Cancer Prevention
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• 제16권14호
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• pp.6099-6104
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• 2015

Background: Previous studies investigating the association between miR-34b/c rs4938723 polymorphism and cancer risk showed inconclusive. Here, we performed meta-analysis to investigate the association between miR- 34b/c rs4938723 polymorphism and digestive cancer risk. Materials and Methods: Literature database including PubMed, OVID, Chinese National Knowledge Infrastructure (CNKI) were searched for publications concerning the association between the miR-34b/c rs4938723 polymorphism and digestive cancer risk. Results: A total of 6 studies consisting of 3246 cases and 3568 controls were included in this meta-analysis. The combined analysis suggested the miR-34b/c rs4938723 polymorphism significantly reduced digestive cancer risk under allelic model, homogeneous co-dominant model and recessive model (C vs T: OR=0.88, 95%CI=0.82-0.95, p-value=0.001; CC vs TT: OR =0.67, 95%CI=0.57-0.80, p-value=0.000; CC vs TT/TC: OR=0.68, 95%CI=0.58-0.80, p-value=0.000). Q-test and I2 test revealed no significant heterogeneity in all genotype comparisons. The Begger's funnel plot and Egger's test did not show significant publication bias. Conclusions: The current evidence supports the conclusion that the miR-34b/c rs4938723 polymorphism decreases an individual's susceptibility to digestive cancers.

• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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• pp.7251-7255
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• 2014

MicroRNAs (miRNAs) act as tumor suppressors or promoters in neoplasia by regulating relative geneexpression. The association between a single nucleotide polymorphism (SNP) rs4938723 in miR-34b/c and susceptibility to cancers was inconsistent in previous studies. In this study, we conducted a literature search of PubMed, Web of Science and Embase to identify all relevant studies in this meta-analysis with 6,036 cases and 6,204 controls. We found that the miR-34b/c rs4938723 polymorphism was significantly associated with increased risk of cancers in the heterozygous model (TC versus TT, OR=1.09, 95% CI=1.01-1.18, P=0.02). Subgroup analysis also revealed increased risk for Asian ethnicity in the heterozygous model (TC versus TT, OR=1.12, 95% CI=1.02-1.22, P=0.02), but decreased risk of colorectal cancer in homozygote model (CC versus TT, OR=0.66, 95% CI=0.47-0.92, P=0.02) and in the recessive model (CC versus TC+TT, OR=0.67, 95% CI=0.48-0.93, P=0.02) by cancer type. The current meta-analysis indicated that the miR-34b/c rs4938723 polymorphism may decrease susceptibility to colorectal cancer. Well-designed studies with larger sample size are required to further validate the results.

• 대한본초학회지
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• 제34권6호
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• pp.71-78
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• 2019

Objective : The purpose of the study was to identify expression profiling of miRNAs associated with cancers after treating allergen-removed Rhus Verniciflua Stokes and allergen-removed Rhus Verniciflua Stokes fumigaed Angelica gigas on leukemia cell lines. Methods : miRNA expression has been analyzed using miRNA array method through denaturation and hybridization after isolating the total RNA from leukemic cell line treated with 100 ㎍/㎖ of aRVS and aRVS-A each. Microarray expressions were interpreted as 'significant' on miRNAs when decreased less than 0.5 fold or increased more than 1.5 fold compared with the control group. Results : Among 158 miRNAs in total, 32 miRNAs were significantly presented in miRNAs expression. miRNA has been activated with a variety of genes for predicted targets, and the overexpressed miRNAs were categorized according to proliferation and metastasis of cancer in this study. The findings were reported that seven miRNAs (let-7b, miR-193a-5p, 296-3p, 26a, 22, 124a, 92b) showed significant expressions on proliferation and growth, seven miRNAs (miR-193a-5p, 26a, 200c, 183, 124a, 198, 210) presented meaningful expressions on invasion and metastasis, two miRNAs (let-7b, miR-210) were highly expressed on angiogenesis, five miRNAs (let-7b, miR-26a, 181d, 181c, 296-5p) related with apoptosis, and six miRNAs (let-7b, miR-200c, 183, 370, 124a, 191) were associated with prognosis of cancer and early diagnostic factors for cancer. Conclusion : The mechanism of miRNA takes a role in diagnosis, treatment, and prognotic factors for cancer as well. This study suggested that further detailed research on overexpression of specific miRNA should be carried out continuously in the future.

• Asian Pacific Journal of Cancer Prevention
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• 제17권sup3호
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• pp.219-224
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• 2016

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver making up more than 80 percent of cases. It is known to be the sixth most prevalent cancer and the third most frequent cause of cancer related death worldwide. Epigenetic regulation constitutes an important mechanism by which dietary components can selectively activate or inactivate target gene expression. The miR-34 family members including mir-34a, mir-34b and mir-34c are tumor suppressor micro RNAs, which are expressed in the majority of normal tissues. Several studies have indicated silencing of miR-34 expression via DNA methylation in multiple types of cancers. Bioactive nutrients like curcumin (Cur) have excellent anticarcinogenic activity and minimal toxic manifestations in biological systems. This compound has recently been determined to induce epigenetic changes. However, Cur is lipophilic and has a poor systemic bioavailability and poor absorption. Its bioavailability is increased through employing dendrosome nanoparticles. The aim of the current study was to investigate the effect of dendrosomal nanocurcumin (DNC) on expression of mir-34 family members in two HCC cell lines, HepG2 and Huh7. We performed the MTT assay to evaluate DNC and dendrosome effects on cell viability. The ability of DNC to alter expression of the mir-34 family and DNA methyltransferases (DNMT1, DNMT3A and 3B) was evaluated using semi-quantitative and quantitative PCR. We observed the entrance of DNC into HepG2 and Huh7 cells. Gene expression assays indicated that DNC treatment upregulated mir34a, mir34b and mir34c expression (P<0.05) as well as downregulated DNMT1, DNMT3A and DNMT3B expression (P<0.05) in both HepG2 and Huh7 cell lines. DNC also reduced viability of Huh7 and HepG2 cells through restoration of miR-34s expression. We showed that DNC could awaken the epigenetically silenced miR-34 family by downregulation of DNMTs. Our findings suggest that DNC has potential in epigenetic therapy of HCC.

• BMB Reports
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• 제46권6호
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• pp.316-321
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• 2013

Gastric cancer remains the main cause of cancer death all around the world, and upregulated activation of the nonreceptor tyrosine kinase c-SRC (SRC) is a key player in the development. In this study, we found that expression of Src is also increased in clinical gastric cancer samples, with the protein level increased more significantly than that at the RNA level. Further study revealed that miR34a and miR203, two tumor suppressive miRNAs, inversely correlate with the expression of Src. Restoration of miR34a and miR203 decreased Src expression in gastric cancer cell lines, which in turn inhibited cell growth and cell migration. In summary, our study here revealed that posttranscriptional regulation of Src contributes to the deregulated cell growth and metastasis in gastric cancer, and targeting Src by miR34a or miR203 mimics would be a promising strategy in therapy.

• 한국수산과학회지
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• 제34권2호
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• pp.137-144
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• 2001

Sequences of partial 18S rDNA have been analyzed to elucidate genetic diversity of scallops collected around Korean sea, The scallops used in genetic comparison are Argopecten irradians concentricus, Amusium japonicum japonicum, Chlamys farreri farreri, Chlamys (Swiftopecten) swifti and Patinopecten yessoensis. The 18S rDNA sequences were aligned by Clustalx program. Phylogenetic tree was drawn by Treecon program, The scallops were divided into two groups-the Family Pectinidae containing A. japonicum japonicum and the Family Propeamussiidae containing Argopecten, Chlamys and Patinopecten genera. The Family Propeamussiidae was also divided into the Supergenera Aequipecten containing A. irradians concentricus and Supergenera Chlamys containing C. farreri farreri, C. swifti and P. yessoensis. The species of C. swifti was closer to the P. yessoensis rather than C. farreri farreri in respect to nuclear 18S rDNA sequence.

• 대한화장품학회지
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• 제41권2호
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• pp.97-103
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• 2015

최근까지 Chromameter$^{(R)}$ CR-400, Mexameter$^{(R)}$ M18 그리고 육안평가는 피부색 평가를 위한 주된 평가방법으로 이용되어 왔다. 하지만 본 연구를 통해 피부색의 변화를 평가할 수 있는 객관성 있는 평가방법으로 이미지 분석을 제안하고자 한다. 본 연구에서는 세 가지의 기존 평가방법의 변수들과 이미지 분석을 통해 얻은 V (Value) 값을 이용하여 미백 인체 효능평가를 수행하고 변수들 사이의 상관성을 분석하여 이미지 분석의 신뢰성을 확보하고자 하였다. 효능 평가를 위해 과색소침착으로 고민하는 34명의 시험 대상자를 모집하였고 선정된 시험 대상자들은 8주간의 시험기간 동안 vitamin C가 함유된 5 종류의 미백 화장품을 사용하는 동시에 일주일에 1회 전기이온영동(iontophoresis) 시술을 받았다. 제품 사용 및 시술 전과 8주 후 기존 평가 변수들과 V 값 측정결과를 비교하고 각 변수들 사이의 상관성을 분석한 결과, 제품 사용 및 시술 8주 후 V 값은 Chromameter$^{(R)}$의 $L^*$ 값의 경향과 유사하게 증가하였으며, $L^*$ 값과는 양의 상관관계를 보이는 것을 확인하였다(r = 0.494, p < 0.01). 또한, Mexameter$^{(R)}$의 MI 값(r = - 0.683, p < 0.01)과 육안평가 측정 값(r = - 0.549, p < 0.01)은 V 값과 음의 상관관계를 나타내었다. 따라서 이미지 분석의 V 값의 활용은 기존의 평가방법과 더불어 주관적인 육안평가의 한계를 보완할 수 있는 신뢰성 있는 미백평가 방법의 하나라고 생각된다.