• Asian Pacific Journal of Cancer Prevention
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• 제16권12호
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• pp.4937-4944
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• 2015

MicroRNAs (miRNAs) are emerging as critical regulators in carcinogenesis and tumor progression. Recently, miR-99a has been reported as a tumor suppressor gene in various human cancers, but its functions in the context of anaplastic thyroid cancer (ATC) remain unknown. In this study, we reported that miR-99a was commonly downregulated in ATC tissue specimens and cell lines with important functional consequences. Overexpression of miR-99a not only dramatically reduced ATC cell viability by inducing cell apoptosis and accumulation of cells at G1 phase, but also inhibited tumorigenicity in vivo. We then screened and identified a novel miR-99a target, mammalian target of rapamycin (mTOR), and it was further confirmed by luciferase assay. Up-regulation of miR-99a would markedly reduce the expression of mTOR and its downstream phosphorylated proteins (p-4E-BP1 and p-S6K1). Similar to restoring miR-99a expression, mTOR down-regulation suppressed cell viability and increased cell apoptosis, whereas restoration of mTOR expression significantly reversed the miR-99a antitumor activity and the inhibition of mTOR/p-4E-BP1/p-S6K1 signal pathway profile. In clinical specimens and cell lines, mTOR was commonly overexpressed and its protein levels were statistically inversely correlated with miR-99a expression. Taken together, our results demonstrated for the first time that miR-99a functions as a tumor suppressor and plays an important role in inhibiting the tumorigenesis through targeting the mTOR/p-4E-BP1/p-S6K1 pathway in ATC cells. Given these, miR-99a may serve as a novel prognostic/diagnostic and therapeutic target for treating ATC.

• Asian Pacific Journal of Cancer Prevention
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• 제17권8호
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• pp.3959-3962
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• 2016

The ten-eleven-translocation-2 (TET2) gene is a novel tumor suppressor gene involved in several hematological malignancies of myeloid and lymphoid origin. Besides loss-of-function mutations and deletions, hypermethylation of the CpG island at the TET2 promoter has been found in human cancers. The TET2 encoded protein regulates DNA methylation. The present study aimed to examine DNA promoter methylation of TET2 in 100 childhood acute lymphoblastic leukemia (ALL) cases and 120 healthy children in southeast Iran. In addition, mRNA expression levels were assessed in 30 new cases of ALL and 32 controls. Our ndings indicated that promoter methylation of TET2 signi cantly increases the risk of ALL (OR=2.60, 95% CI=1.31-5.12, p=0.0060) in comparison with absent methylation. Furthermore, the TET2 gene was signi cantly downregulated in childhood ALL compared to healthy children (p=0.0235). The results revealed that hypermethylation and downregulation of TET2 gene may play a role in predisposition to childhood ALL. Further studies with larger sample sizes and different ethnicities are needed to con rm our ndings.

• Toxicological Research
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• 제16권1호
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• pp.59-61
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• 2000

A single nucleotide polymorphism in the transforming growth factor-$\beta$ type II receptor (TGE$\beta$RII) gene of the rat was studied. TGF$\beta$RII is a tumor suppressor that is frequently inactivated by mutation in human colon cancers. A novel nucleotide polymorphism of G to A(or A to G), which causes a silent mutation at codon 129, was found in G:C rich sequence in the TGF$\beta$RII gene of Sprague-Dawley rats. The results suggest that genetic polymorphism occures without a strain of the laboratory animal.

• BMB Reports
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• 제45권11호
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• pp.604-611
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• 2012

Recent advances in genome and transcriptome analysis have enabled identification of numerous members of a new class of noncoding RNA, long noncoding RNA (lncRNA). lncRNAs are broadly defined as RNA molecules greater than 200 nt in length and lacking an open reading frame. Recent studies provide evidence that lncRNAs play central roles in a wide range of cellular processes through interaction with key component proteins in the gene regulatory system, and that alteration of their cell- or tissue-specific expression and/or their primary or secondary structures is thought to promote cell proliferation, invasion and metastasis. The biological and molecular characteristics of the large majority of lncRNAs remains unknown, and it is anticipated that improved understanding of the roles played by lncRNAs in cancer will lead to the development of novel biomarkers and effective therapeutic strategies.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2003년도 춘계학술대회 논문집
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• pp.83-83
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• 2003

Mutations of p53 tumor suppressor gene have been associated with exposure to carcinogens. Cultured human breast epithelial cells (MCF10A) were treated with Benzo(a)pyrene(BaP) or N-Methyl-N'-nitro-N-nitrosoguanidine(MNNG). MCF10A cells were grown in DMEM/F12 medium and trated for 6, 12, 24, 48 and 96h with Bap (1, 10 and 100 $\mu$M) dissolved in dimethylsulfoxide(DMSO). (omitted)

• 대한의생명과학회지
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• 제18권4호
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• pp.413-419
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• 2012

The melanoma differentiation-associated gene-7 (MDA-7) protein, also known as interleukin-24 (IL-24), is a novel candidate of tumor suppressor that can induce apoptosis experimentally in a variety of human malignant cells. However, there have been few studies about its role in colorectal cancer. We performed immunohistochemical detection of MDA-7/IL-24 in 399 tissue samples from primary colorectal adenocarcinoma patients using a tissue microarray. Western blotting was then done to confirm the immunohistochemical observations. MDA-7/IL-24 immunoreactivity was observed in 116 (29.1%) of the 399 colorectal adenocarcinoma cases. Analysis of the MDA-7/IL-24 expression by Western blotting confirmed the immunohistochemical results. The tumors with a negative MDA-7/IL-24 expression more frequently showed poor differentiation (P=0004), lymph node metastasis (P=0.001), deep invasion (P=0.008) and high stage (P=0.001). A subset of colorectal adenocarcinoma revealed a decreased expression of MDA-7/IL-24, and this was associated with progressive pathologic features. These findings suggest that loss of MDA-7/IL-24 expression may play a role in tumor growth and progression of colorectal adenocarcinomas.

• 한국식품위생안전성학회지
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• 제11권1호
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• pp.71-75
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• 1996

In order to study the antitumoral effect of Selaginella tamariscina extracts, the cytotoxicities to human histiocytic leukemia cells (U937) and lymphocyte were measured by MTT method. The water extract of Selaginella tamariscina was partitioned into chloroform (CHCl3), ethylacetate (EtAc), n-butanol (BuOH) and water (H2O), successively. CHCl3, EtAc and BuOH fractions of Selaginella tamariscina showed the cytotoxicity to the U937 cells but they had effect on the cytotoxicity of lymphocyte under the same conditions. The tumor-specific cytotoxicity of Selaginella tamariscina fractions migh have been attributed to their genotoxic effect on actively proliferating cells. The expression of p53 tumor suppressor gene was then evaluated by northern blotting. The increased expression of p53 was induced by Selaginella tamariscina fraction V but no expression of p53 was induced by CHCl3, EtAc, and BuOH fractions of Selaginella tamariscina water extract (fraction V) should be required for the cytotoxcity on U937 and the other fractions of Selaginella tamariscina mediated the U937 disruption.

• Asian Pacific Journal of Cancer Prevention
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• 제15권15호
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• pp.6243-6246
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• 2014

To investigate the role of miR-1297 and the tumor suppressor gene PTEN in cell proliferation of testicular germ cell tumors (TGCT). MTT assays were used to test the effect of miR-1297 on proliferation of the NCCIT testicular germ cell tumor cell line. In NCCIT cells, the expression of PTEN was assessed by Western blotting further. In order to confirm target association between miR-1297 and 3'-UTR of PTEN, a luciferase reporter activity assay was employed. Moreover, roles of PTEN in proliferation of NCCIT cells were evaluated by transfection of PTEN siRNA. Proliferation of NCCIT cells was promoted by miR-1297 in a concentration-dependent manner. In addition, miR-1297 could bind to the 3'-UTR of PTEN based on luciferase reporter activity assay, and reduced expression of PTEN at protein level was found. Proliferation of NCCIT cells was significantly enhanced after knockdown of PTEN by siRNA. miR-1297 as a potential oncogene could induce cell proliferation by targeting PTEN in NCCIT cells.

• Journal of Gastric Cancer
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• 제3권3호
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• pp.145-150
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• 2003

Purpose: The p53 tumor suppressor gene is believed to play a pivotal role in preventing the uncontrolled cellular growth characteristic of cancer. Mutation of the p53 gene represent one of the most common genetic alterations in human cancers, and the acquisition of such defects is strongly associated with tumor progression and metastasis. The aim of this study was to evaluate the relation between p53 immunoreactivity and the mutation of p53 gene in gastric adenocarcinoma obtained by laser capture microscope. Materials and Methods: Formalin fixed paraffin embedded tissue specimens were obtained from 20 patients who underwent surgery for gastric cancer. According to UICC TNM system, 3 of the cases were Ia, 2 cases II, 4 cases IIIa, 5 cases IIIb, and 6 cases IV. Results: Immunohistochemical staining revealed eight cases as negative (less than $10\%$), twelve cases as postive (more than $10\%$). The locations of mutations were as follows; 7 cases had point mutation at exon 4, and 3 cases point mutation at exon 8. There was no mutation at exon 5, 6, 7 and 9. The mutation was observed in 1 case out of 8 p53 oncoprotein negative cases, and 7 cases out of 12 p53 positive cases. The mutation was more common in p53 positive cases (P<0.05), However, there was no significant correlation between p53 mutation observed by DNA sequencing after laser capture microdissection and expression of p53 oncoprotein. Conclusion: These result suggest that he expression of p53 oncoprotein not to be related to the mutation of p53 gene at exons 4 through 9 in gastric cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제13권9호
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• pp.4689-4693
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• 2012

Lung cancer is the most common type of cancer and one of the leading causes of death in the world. Genetic factors play an important role in its development. PDCD6, the encoding gene for programmed cell death protein 6, may function as a tumor suppressor gene. Non-small cell lung cancer (NSCLC) contributes about 80% to newly histologically diagnosed lung cancer patients. To explore the relationship between PDCD6 and NSCLC, we examined two single nucleotide polymorphisms(rs3756712 G/T andrs4957014 G/T, both in the intron region) of the PDCD6gene.A hospital-based case-control study was carried out including 302 unrelated NSCLC patients and 306 healthy unrelated subjects. Significantly increased NSCLC risk was found to be associated with the T allele of rs4957014 (P=0.027, OR=0.760, 95%CI=0.596-0.970). The genotype and allele frequencies of rs3756712 did not shown any significant difference between NSCLC group and controls (P=0.327, OR=0.879, 95%CI=0.679-1.137). In conclusion, we firstly demonstrated the association between the PDCD6 gene and risk of NSCLC in a Chinese Han population.