• Title/Summary/Keyword: miR-34c

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Protective Role of miR-34c in Hypoxia by Activating Autophagy through BCL2 Repression

  • Kim, Soyoung;Han, Jaeseok;Ahn, Young-Ho;Ha, Chang Hoon;Hwang, Jung Jin;Lee, Sang-Eun;Kim, Jae-Joong;Kim, Nayoung
    • Molecules and Cells
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    • v.45 no.6
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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.

Differential Expression of miR-34c and Its Predicted Target Genes in Testicular Tissue at Different Development Stages of Swine

  • Zhang, Xiaojun;Zhao, Wei;Li, Chuanmin;Yu, Haibin;Qiao, YanYan;Li, Aonan;Lu, Chunyan;Zhao, Zhihui;Sun, Boxing
    • Asian-Australasian Journal of Animal Sciences
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    • v.28 no.11
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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.

MiR-34b/c rs4938723 Polymorphism Significantly Decreases the Risk of Digestive Tract Cancer: Meta-analysis

  • Ji, Tian-Xing;Zhi, Cheng;Guo, Xue-Guang;Zhou, Qiang;Wang, Guo-Qiang;Chen, Bo;Ma, Fei-Fei
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.14
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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.

Association between a Polymorphism in miR-34b/c and Susceptibility to Cancer - a Meta-analysis

  • Lin, Zhuo;Chen, Li;Song, Mei;Shi, Ke-Qing;Tang, Kai-Fu
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.17
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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.

MicroRNA Expression in Leukemia Cell Line(K562 cell) Using Rhus Verniciflua Stokes (건칠(乾漆)을 이용한 K562 만성 골수성 백혈병 세포주에서의 MicroRNA 발현 규명)

  • Choi, Hyun Sook
    • The Korea Journal of Herbology
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    • v.34 no.6
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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.

Evaluation of MiR-34 Family and DNA Methyltransferases 1, 3A, 3B Gene Expression Levels in Hepatocellular Carcinoma Following Treatment with Dendrosomal Nanocurcumin

  • Chamani, Fatemeh;Sadeghizadeh, Majid;Masoumi, Mahbobeh;Babashah, Sadegh
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.sup3
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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.

Posttranscriptional deregulation of Src due to aberrant miR34a and miR203 contributes to gastric cancer development

  • Hao, Qiang;Lu, Xiaozhao;Liu, Nannan;Xue, Xiaochang;Li, Meng;Zhang, Cun;Qin, Xin;Li, Weina;Shu, Zhen;Song, Bin;Wang, Qing;Song, Liqiang;Zhang, Wei;Zhang, Yingqi
    • BMB Reports
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    • v.46 no.6
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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.

Sequence Analysis of the 18S rDNA from Scallops Collected around Korean Sea (한국 주변해역 가리비로부터 분리한 18S rDNA의 염기서열 분석)

  • KIM Mi-Jung;JM Long-Guo;JIN Hyung-Joo;CHO Ji-Young;PARK Jung-Youn;CHANG Young Jin;HONG Yong-Ki
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.34 no.2
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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.

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A Comparison Study Between Image Analysis and Conventional Methods in the Evaluation of Asian Skin Color (아시아 피부에서 기존 미백 평가방법과 이미지 분석방법의 비교연구 (비타민 C 제형의 이온토포레시스 연구))

  • Park, Hye Kyong;Kim, Nam Soo;Moon, Tae Kee;Kim, Bora;Jung, Ho Young
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.41 no.2
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    • pp.97-103
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    • 2015
  • Until recently, the three conventional evaluation methods, which are instrumental (Chromameter$^{(R)}$ CR-400 and Mexameter$^{(R)}$ M18) and visual assessments have been used frequently for skin color evaluation. However, we took notice the potential of image analysis as a new tool to evaluate color change of skin. To reveal the reliability of the image analysis for the evaluation of whitening agents, 34 healthy female volunteers with hyperpigmentation were recruited, and the selected volunteers applied the whitening products containing Vitamin C twice a day in the morning and evening and received iontophoresis treatments once a week for 8 weeks. The changes in hyperpigmentation evaluated by Chromameter$^{(R)}$, Mexameter$^{(R)}$ and visual assessment were compared with the results from the image analysis. As with $L^*$ value trends of the analysis using Chromameter$^{(R)}$, the V value from the image analysis increased after applying the test products compared with baseline values. Furthermore, V value showed a positive correlation with $L^*$ value (r = 0.494, p < 0.01) and negative correlation with MI (r = - 0.683, p < 0.01) and VG (r = - 0.549, p < 0.01). Therefore, image analysis may be considered as an effective method to complement the limitations of visual assessment for whitening efficacy in Asians.

Coupling of ent-Cyclic Peroxide and Ircinol A, Two Biologically Active Natural Marine Products

  • Lim, Chi-Won;Kim, Yeun-Kye;Jang, Mi-Soon;Park, Jin-Il;Park, Hee-Yeun
    • Fisheries and Aquatic Sciences
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    • v.9 no.4
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    • pp.175-178
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    • 2006
  • An acidic ent-cyclic peroxide was isolated from a sponge, Plakotis sp., and showed activity against leishmaniasis and pathogenic fungi. To improve the activity of this compound, we coupled the acidic ent-cyclic at the C1 position of ircinol A. Compound 3 exhibited significant activity against Leishmania mexican a and fungi with $IC_{50}$ values of 0.7 and $0.3-34{\mu}g/mL$, respectively. The yield of compound 3 was 98%.