• Journal of Microbiology and Biotechnology
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• 제27권8호
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• pp.1367-1378
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• 2017

Epigenetic alterations such as DNA methylation, histone acetylation, and chromatin remodeling can control gene expression by regulating gene transcription. DNA methylation is one of the frequent epigenetic events that play important roles in cancer development. Cancer cells can gain significant resistance to anticancer drugs and escape programmed cell death through major epigenetic changes, including DNA methylation. To date, several research groups have identified instances of both (i) hypermethylation of tumor suppressor genes, and (ii) global hypomethylation of oncogenes. These changes in DNA methylation status could be used as biomarkers for the diagnosis and prognosis of cancer patients undergoing chemotherapies or other clinical therapies. Herein, we describe genes for which methylation is dependent upon anticancer drug resistance in patients with gastric cancer; we then suggest a significant epigenetic target to focus on for overcoming anticancer drug resistance.

• BMB Reports
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• 제55권2호
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• pp.81-86
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• 2022

Macrophages are a major cellular component of innate immunity and are mainly known to have phagocytic activity. In the tumor microenvironment (TME), they can be differentiated into tumor-associated macrophages (TAMs). As the most abundant immune cells in the TME, TAMs promote tumor progression by enhancing angiogenesis, suppressing T cells and increasing immunosuppressive cytokine production. N-myc downstream-regulated gene 2 (NDRG2) is a tumor suppressor gene, whose expression is down-regulated in various cancers. However, the effect of NDRG2 on the differentiation of macrophages into TAMs in breast cancer remains elusive. In this study, we investigated the effect of NDRG2 expression in breast cancer cells on the differentiation of macrophages into TAMs. Compared to tumor cell-conditioned medium (TCCM) from 4T1-mock cells, TCCM from NDRG2-over-expressing 4T1 mouse breast cancer cells did not significantly change the morphology of RAW 264.7 cells. However, TCCM from 4T1-NDRG2 cells reduced the mRNA levels of TAM-related genes, including MR1, IL-10, ARG1 and iNOS, in RAW 264.7 cells. In addition, TCCM from 4T1-NDRG2 cells reduced the expression of TAM-related surface markers, such as CD206, in peritoneal macrophages (PEM). The mRNA expression of TAM-related genes, including IL-10, YM1, FIZZ1, MR1, ARG1 and iNOS, was also downregulated by TCCM from 4T1-NDRG2 cells. Remarkably, TCCM from 4T1-NDRG2 cells reduced the expression of PD-L1 and Fra-1 as well as the production of GM-CSF, IL-10 and ROS, leading to the attenuation of T cell-inhibitory activity of PEM. These data showed that compared with TCCM from 4T1-mock cells, TCCM from 4T1-NDRG2 cells suppressed the TAM differentiation and activation. Collectively, these results suggest that NDRG2 expression in breast cancer may reduce the differentiation of macrophages into TAMs in the TME.

• Molecules and Cells
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• 제39권8호
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• pp.619-624
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• 2016

Glioblastoma stem cells (GBM-SCs) are believed to be a subpopulation within all glioblastoma (GBM) cells that are in large part responsible for tumor growth and the high grade of therapeutic resistance that is so characteristic of GBM. MicroRNAs (miR) have been implicated in regulating the expression of oncogenes and tumor suppressor genes in cancer stem cells, including GBM-SCs, and they are a potential target for cancer therapy. In the current study, miR-203 expression was reduced in $CD133^+$ GBM-SCs derived from six human GBM biopsies. MicroRNA-203 transfected GBM-SCs had reduced capacity for self-renewal in the cell sphere assay and increased expression of glial and neuronal differentiation markers. In addition, a reduced proliferation rate and an increased rate of apoptosis were observed. Therefore, miR-203 has the potential to reduce features of stemness, specifically in GBM-SCs, and is a logical target for GBM gene therapy.

• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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• pp.6989-6999
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• 2014

Colorectal cancer (CRC) is one of the major healthcare problems worldwide and its processes of genesis include a sequence of molecular pathways from adenoma to carcinoma. The discovery of microRNAs, a subset of regulatory non-coding RNAs, has added new insights into CRC diagnosis and management. Together with several causes of colorectal neoplasia, aberrant expression of oncomiRs (oncogenic and tumor suppressor miRNAs) in cancer cells was found to be indirectly result in up- or down-regulation of targeted mRNAs specific to tumor promoter or inhibitor genes. The study of miRNAs as CRC biomarkers utilizes expression profiling methods from traditional tissue samples along with newly introduced non-invasive samples of faeces and body fluids. In addition, miRNAs could be employed to predict chemo- and radio-therapy responses and be manipulated in order to alleviate CRC characteristics. The scope of this article is to provide a comprehensive review of scientific literature describing aberrantly expressed miRNAs, and consequently dysregulation of targeted mRNAs along with the potential role of miRNAs in CRC diagnosis and prognosis, as well as to summarize the recent findings on miRNA-based manipulation methods with the aim of advancing in anti-CRC therapies.

• Annals of Coloproctology
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• 제34권6호
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• pp.280-285
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• 2018

For many years, developmental and physiological differences have been known to exist between anatomic segments of the colorectum. Because of different outcomes, prognoses, and clinical responses to chemotherapy, the distinction between right colon cancer (RCC) and left colon cancer (LCC) has gained attention. Furthermore, variations in the molecular features and gut microbiota between right and LCCs have recently been a hot research topic. CpG island methylator phenotype-high, microsatellite instability-high colorectal cancers are more likely to occur on the right side whereas tumors with chromosomal instability have been detected in approximately 75% of LCC patients and 30% of RCC patients. The mutation rates of oncogenes and tumor suppressor genes also differ between RCC and LCC patients. Biofilm is more abundant in RCC patients than LLC patients, as are Prevotella, Selenomonas, and Peptostreptococcus. Conversely, Fusobacterium, Escherichia/Shigella, and Leptotrichia are more abundant in LCC patients compared to RCC patients. Distinctive characteristics are apparent in terms of molecular features and gut microbiota between right and LCC. However, how or to what extent these differences influence diverging oncologic outcomes remains unclear. Further clinical and translational studies are needed to elucidate the causative relationship between primary tumor location and prognosis.

• 대한의생명과학회지
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• 제28권2호
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• pp.92-100
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• 2022

Ginkgo biloba Leaf Extract (GBE) is an extract from leaves of the Ginkgo biloba tree, widely used as a health supplement. GBE can inhibit the proliferation of several types of tumor cell. Although it is known to have anti-cancer effects in breast cancer and skin cancer, research related to gastric cancer is still insufficient. Based on results showing anti-cancer effects on solid cancer, we aimed to determine whether GBE has similar effects on gastric cancer. In this study, the anti-cancer effect of GBE in gastric adenocarcinoma was investigated by confirming the cell proliferation inhibitory effect of AGS cells. We also evaluated whether GBE regulates expression of the tumor suppressor protein p53 and Rb. GBE has apoptotic effects on AGS cells that were confirmed by changes in anti-apoptosis protein Bcl-2, Bcl-xl and pro-apoptosis protein Bax levels. Wound healing and cell migration were also decreased by treatment with GBE. Furthermore, we verified the effects of GBE on mitogenic signaling by investigating AKT target gene expression levels and revealed downregulated Sod2 and Bcl6 expression. We also confirmed that expression of inflammation-related genes decreased in a time-dependent manner. These results indicate that GBE has an anti-cancer effect on human gastric cancer cell lines. Further research on the mechanism of the anti-cancer effect will serve as basic data for possible anti-cancer drug development.

• BMB Reports
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• 제55권8호
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• pp.380-388
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• 2022

The B cell translocation gene 1 (BTG1) and BTG2 play a key role in a wide range of cellular activities including proliferation, apoptosis, and cell growth via modulating a variety of central biological steps such as transcription, post-transcriptional, and translation. BTG1 and BTG2 have been identified by genomic profiling of B-cell leukemia and diverse lymphoma types where both genes are commonly mutated, implying that they serve as tumor suppressors. Furthermore, a low expression level of BTG1 or BTG2 in solid tumors is frequently associated with malignant progression and poor treatment outcomes. As physiological aspects, BTG1 and BTG2 have been discovered to play a critical function in regulating quiescence in hematopoietic lineage such as Hematopoietic stem cells (HSCs) and naive and memory T cells, highlighting their novel role in maintaining the quiescent state. Taken together, emerging evidence from the recent studies suggests that BTG1 and BTG2 play a central anti-proliferative role in various tissues and cells, indicating their potential as targets for innovative therapeutics.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제27권6호
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• pp.483-490
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• 2001

There were many controversies in the cause and progress of tumorigenesis. Recently, studies on the mutation of genes related to the tumor have extensively been performed due to development of molecular biology. Structural and morphological changes of chromosomes, which are related to the abnormal activation of oncogenes or inactivation of tumor suppression genes, transform the normal cells into the tumor cells. p53 and Rb are well known tumor suppressor genes, while oncogenes include c-myc, bcl-2 and ras, etc. When exposed to cell damaging agents, p53 inhibits cell growth by inducing transcription of p21. Especially p73, which is homo-logy of p53, frequently deleted in melanoma, neuroblastoma, colon cancer, and breast cancer, when over produced, p73 activates the transcription of p21, bax-1 and inhibits cell growth by inducing apoptosis. For study on mRNA expression of p21 and p73, normal oral keratinocytes, and cell lines of primary and metastatic oral squamous cell carcinoma were cultured and then electrophoresis and RT-PCR(reverse transcription-polymerase chain reaction) were performed. 1. The mRNA of p21 and p73 in normal oral keratinocyte expressed lower than that of primary squamous cell carcinoma. 2. The mRNA of p21 in metastatic oral squamous carcinoma cell lines was expressed as various patterns compared with that of normal oral keratinocyte. 3. In the metastatic oral squamous cell lines, the mRNA of HN8 expressed higher than that of HN12 or HN19. 4. The mRNA of p73 in primary oral squamous cell lines expressed 4-5 times higher than that of normal keratinocyte. 5. In metastatic oral squamous cell lines, there was no significant expression of p73 mRNA compared with that of normal oral keratinocyte. From the results obtained in this study, mRNA expression of p73 in primary oral squamous cell lines was remarkable, while mRNA expression of p21 and p73 in metastatic oral squamous cell lines were statistically insignificant.

• Asian Pacific Journal of Cancer Prevention
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• 제17권sup3호
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• pp.155-160
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• 2016

Breast cancer (BC) is the second most common cancer in the world and by far the most frequent cancer among women, with an estimated 1.67 million new cancer cases diagnosed in 2012 (25% of all cancers). Polygene expression analysis is used to predict the prognosis and determine the most appropriate treatment regimen. The objective of this study was to examine the gene expression profiles of SIRT3, HRAS, LSP1, SCUBE2 and AP2A2 in Iranian women with BC.A total of 136 patients including healthy controls were categorized into three groups based on the relapse of the disease. Expression of desired genes in formalin-fixed, paraffin embedded tissues collected from all groups of participants was analyzed via the RT PCR method. RNA extraction and cDNA synthesis were performed then real-time quantitative PCR was carried out. Gene expression analysis revealed that the expression of SIRT3 was equal among patient and control groups. LSP1 was down regulated in all patient groups relative to controls but reduced expression in the metastatic group relative to the non-metastatic one was not significant. HRAS was significantly overexpressed in total and metastatic tumor samples versus normal but not in non-metastatic cases. SCUBE2 expression showed significant over-expression in both overall tumor samples and the non-metastatic group as compared to normal tissues. Gene expression level of AP2A2 in all groups was not detectable. Our data are compatible with a tumor suppressor role of LSP1 related to potential prognostic factor for tumor recurrence and outcome. This study for the first time assayed the prognostic value and changes in the expression of SIRT3, LSP1, HRAS, SCUBE2 and AP2A2 genes in women with breast cancer in the Iranian population and findings confirmed potential biomarker and prognostic capability of these genes. Such expression profiling data can critically improve prognosis and treatment decisions in cancer patients.

• Genomics & Informatics
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• 제10권1호
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• pp.40-43
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• 2012

Recent genomewide association studies of large samples have identified genes that are associated with blood pressure. The Global Blood Pressure Genetics (Global BPgen) and Cohorts for Heart and Aging Research in Genome Epidemiology (CHARGE) consortiums identified 14 loci that govern blood pressure on a genomewide significance level, one of which is $CASZ1$ confirmed in both Europeans and Asians. $CASZ1$ is a zinc finger transcription factor that controls apoptosis and cell fate and suppresses neuroblastoma tumor growth by reprogramming gene expression, like a tumor suppressor. To validate the function of $CASZ1$ in blood pressure, we decreased $Casz1$ mRNA levels in mice by siRNA. $Casz1$ siRNA reduced mRNA levels by 59% in a mouse cell line. A polyethylenimine-mixed siRNA complex was injected into mouse tail veins, reducing $Casz1$ mRNA expression to 45% in the kidney. However, blood pressure in the treated mice was unaffected, despite a 55% reduction in $Casz1$ mRNA levels in the kidney on multiple siRNA injections daily. Even though $Casz1$ siRNA-treated mice did not experience any significant change in blood pressure, our study demonstrates the value of $in$ $vivo$ siRNA injection in analyzing the function of candidate genes identified by genomewide association studies.