• Food Science and Preservation
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• v.13 no.1
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• pp.83-87
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• 2006

Gastrodia elata Blume is a major imp0l1ant medicinal resource in Korea. In order to confirm the biological activities of Gastrodia elata Blume, we carried out various in vitro assays. Of them, anti-oxidant and anti-tumor activities were detected from assays. The prototype of Gastrodia elata Blume extracts was used for 1he evaluation of DPPH, FRAP, hydroxyradical scavenging assay as anti-oxidant assays, as well as anti-tumor asctivities as wound assay and invasion assay. As a result, the prototype of Gastrodia elata Blume extracts showed potent anti-oxidative activity and anti-tumor activity in vitro. These above results suggest that 1he Gastrodia elata Blume extracts could have potential to alleviate oxidation process, cell motility activity, and tumorigenesis.

• Molecules and Cells
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• v.39 no.4
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• pp.330-336
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• 2016

Long non-coding RNAs (lncRNAs) are involved in multiple cellular events, as well as in tumorigenesis. Colon cance-rassociated transcript-1 (CCAT1) gene encodes an lncRNA whose over-activation was observed in an expanding list of primary human solid tumors and tumor cell lines, however its biological roles in acute myeloid leukaemia (AML) has not been reported yet at present. In this study, the aberrant upregulation of CCAT1 was detected in French-American-British M4 and M5 subtypes of adult AML patients. By gain- and loss-of-function analysis, we determined that CCAT1 repressed monocytic differentiation and promoted cell growth of HL-60 by sequestering tumor suppressive miR-155. Accordingly, a significant decrease in miR-155 level was detected in AML patients. Reintroduction of miR-155 into HL-60 cells restored monocytic maturation and repressed cell proliferation. Furthermore, CCAT1 could up-regulated c-Myc via its competing endogenous RNA (ceRNA) activity on miR-155. In conclusion, these results revealed new mechanism of lncRNA CCAT1 in AML development, and suggested that the manipulation of CCAT1 expression could serve as a potential strategy in AML therapy.

• Molecules and Cells
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• v.41 no.2
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• pp.93-102
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• 2018

Discoidin domain receptor 1 (DDR1) is involved in tumorigenesis and angiogenesis. However, its role in lymphangiogenesis has been unknown. Here, we tested whether downregulation of DDR1 expression by miR-199a/b can suppress lymphangiogenesis. We also aimed to identify miRNA target site(s) in the 3' untranslated region (UTR) of DDR1. Transfection with miR-199a/b-5p mimics reduced expression of DDR1 and tube formation in primary human dermal lymphatic endothelial cells, whereas miR-199a/b-5p inhibitors showed the opposite effects. Critically, injection of miR-199a/b-5p mimics suppressed DDR1 expression and lymphangiogenesis in a corneal alkali-burn rat model. The three well-conserved seed matched sites for miR-199a/b-5p in the DDR1 3'-UTR were targeted, and miRNA binding to at least two sites was required for DDR1 inhibition. Our data suggest that DDR1 promotes enhanced lymphangiogenesis during eye injury, and miR-199a/b-5p suppresses this activity by inhibiting DDR1 expression. Thus, this miRNA may be useful for the treatment of lymphangiogenesis-related eye diseases.

• Korean Journal of Clinical Laboratory Science
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• v.41 no.4
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• pp.180-188
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• 2009

Plakoglobin (PKG) is a protein linking cadherin adhesion receptors to the actin cytoskeleton and its overexpression has been known to suppress cell proliferation and tumorigenesis in thyroid cancer. We investigated the effect of 5-aza-2'-deoxycytidine (5-Aza-CdR), a DNA methyltransferase inhibitor, on the methylation status of the promoter and the expression of the plakoglobin gene in a thyroid carcinoma cell line (ARO) and papillary thyroid carceinoma. In cultures of ARO cell line incubated without 5-Aza-2'-deoxycytidine (5-Aza-CdR), five of the fifteen CpG sites in the promoter spanning -225 and -54 were methylated at 4.2 - 12.5%. When the cells were treated with 5-Aza-CdR, all the methylated CpG sites were induced to be demethylated except one. In addition, a new methylation at one CpG site, CpG4, was identified at level of 12.0%. The expression level of PKG decreased approximately 10-fold in the 5-Aza-CdR treated cells compared to untreated cells. Different pattern of promoter methylation and expression of PKG was also observed in the tissue samples. CpG10 and CpG12 sites were methylated at 9.0-27.0% in normal tissues. However, in cancer tissues, CpG5 and CpG10 sites were methylated at 10.0-22.0%. Three of ten normal thyroid tissue samples and one of thirteen papillary carcinoma tumor samples showed increased PKG mRNA expression level. PKG protein expression analyzed by the immunohistochemical staining showed higher expression in the tumor compared with normal.

• Journal of Gastric Cancer
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• v.16 no.1
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• pp.21-27
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• 2016

Purpose: Transducer-like enhancer of split 1 (TLE1) is a member of the Groucho/TLE family of transcriptional co-repressors that regulate the transcriptional activity of numerous genes. TLE1 is involved in the tumorigenesis of various tumors. We investigated the prognostic significance of TLE1 expression and its association with clinicopathological parameters in gastric cancer (GC) patients. Materials and Methods: Immunohistochemical analysis of six tissue microarrays was performed to examine TLE1 expression using 291 surgically resected GC specimens from the Soonchunhyang University Cheonan Hospital between July 2006 and December 2009. Results: In the non-neoplastic gastric mucosa, TLE1 expression was negative. In GC, 121 patients (41.6%) were positive for TLE1. The expression of TLE1 was significantly associated with male gender (P=0.021), less frequent lymphatic (P=0.017) or perineural invasion (P=0.029), intestinal type according to the Lauren classification (P=0.024), good histologic grade (P<0.001), early pathologic T-stage (P=0.012), and early American Joint Committee on Cancer stage (P=0.022). In the Kaplan-Meier analysis, the TLE1 expression was significantly associated with longer disease-free (P=0.022) and overall (P=0.001) survival rates. Conclusions: We suggested that TLE1 expression is a good prognostic indicator in GCs.

• The Korean Journal of Physiology and Pharmacology
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• v.8 no.1
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• pp.27-31
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• 2004

${\Delta}^{12}-Prostaglandin$ $J_2\;({\Delta}^{12}-PGJ_2)$ is one of cyclopentenone prostaglandins. The ${\Delta}^{12}-PGJ_2$ is known to induce apoptosis of tumor cells, however, it's action mechanism is not clear. It has recently been reported that STAT3 is involved in tumorigenesis. In the present study, we investigated the role of STAT3-interacting protein (STIP1) in the cytotoxicity of ${\Delta}^{12}-PGJ_2$, since STIP1 was recently reported as a modulator of STAT3 activation by specifically binding to inactive (unphosphorylated) STAT3. The effect of ${\Delta}^{12}-PGJ_2$ was observed in stably overexpressing Neuro-2A cells transfected with full cDNA of STIP1, and cytotoxicity of ${\Delta}^{12}-PGJ_2$ in the transfected cells was increased, compared with the vector control cells. The cytotoxicity of ${\Delta}^{12}-PGJ_2$ treatment was significantly accentuated by pretreatment of the STIP1-transfected cells with protein kinase inhibitor, genistein, and less activation of STAT3 in STIP1-transfected cells was shown, compared with the vector control cells. Expression of bax was also increased in the STIP1-transfected cells. These data suggest that STIP1 inhibits cell growth via inhibition of STAT3 activation in ${\Delta}^{12}-PGJ_2$ treatment.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.2
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• pp.131-138
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• 2009

The binding of interleukin-6 (IL-6) cytokine family ligands to the gp130 receptor complex activates the Janus kinase (JAK)/ signal transducer and activator of transcription 3 (STAT3) signal transduction pathway, where STA T3 plays an important role in cell survival and tumorigenesis. Constitutive activation of STAT3 has been frequently observed in many cancer tissues, and thus, blocking of the gp130 signaling pathway, at the JAK level, might be a useful therapeutic approach for the suppression of STAT3 activity, as anticancer therapy. AG490 is a tyrphostin tyrosine kinase inhibitor that has been extensively used for inhibiting JAK2 in vitro and in vivo. In this study, we demonstrate a novel mechanism associated with AG490 that inhibits the JAK/STAT3 pathway. AG490 induced downregulation of gp130, a common receptor for the IL-6 cytokine family compounds, but not JAK2 or STAT3, within three hours of exposure. The downregulation of gp130 was not caused by enhanced degradation of gp130 or by inhibition of mRNA transcription. It most likely occurred by translation inhibition of gp130 in association with phosphorylation of the eukaryotic initiation factor-2 a. The inhibition of protein synthesis of gp130 by AG490 led to immediate loss of mature gp130 in cell membranes, due to its short half-life, thereby resulting in reduction in the STAT3 response to IL-6. Taken together, these results suggest that AG490 blocks the STAT3 activation pathway via a novel pathway.

• Experimental and Molecular Medicine
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• v.50 no.11
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• pp.12.1-12.12
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• 2018

Drugs targeting the epidermal growth factor receptor (EGFR), such as cetuximab and panitumumab, have been prescribed for metastatic colorectal cancer (CRC), but patients harboring KRAS mutations are insensitive to them and do not have an alternative drug to overcome the problem. The levels of ${\beta}$-catenin, EGFR, and RAS, especially mutant KRAS, are increased in CRC patient tissues due to mutations of adenomatous polyposis coli (APC), which occur in 90% of human CRCs. The increases in these proteins by APC loss synergistically promote tumorigenesis. Therefore, we tested KYA1797K, a recently identified small molecule that degrades both ${\beta}$-catenin and Ras via $GSK3{\beta}$ activation, and its capability to suppress the cetuximab resistance of KRAS-mutated CRC cells. KYA1797K suppressed the growth of tumor xenografts induced by CRC cells as well as tumor organoids derived from CRC patients having both APC and KRAS mutations. Lowering the levels of both ${\beta}$-catenin and RAS as well as EGFR via targeting the $Wnt/{\beta}$-catenin pathway is a therapeutic strategy for controlling CRC and other types of cancer with aberrantly activated the $Wnt/{\beta}$-catenin and EGFR-RAS pathways, including those with resistance to EGFR-targeting drugs attributed to KRAS mutations.

• Biomolecules & Therapeutics
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• v.27 no.6
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• pp.553-561
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• 2019

Rab25, a member of the Rab11 small GTPase family, is central to achieving cellular polarity in epithelial tissues. Rab25 is highly expressed in epithelial cells of various tissues including breast, vagina, cervix, the gastrointestinal tract, and skin. Rab25 plays key roles in tumorigenesis, mainly by regulating epithelial differentiation and proliferation. However, its role in skin physiology is relatively unknown. In this study, we demonstrated that Rab25 knock-out (KO) mice show a skin barrier dysfunction with high trans-epidermal water loss and low cutaneous hydration. To examine this observation, we investigated the histology and epidermal differentiation markers of the skin in Rab25 KO mice. Rab25 KO increased cell proliferation at the basal layer of epidermis, whereas the supra-basal layer remained unaffected. Ceramide, which is a critical lipid component for skin barrier function, was not altered by Rab25 KO in its distribution or amount, as determined by immunohistochemistry. Notably, levels of epidermal differentiation markers, including loricrin, involucrin, and keratins (5, 14, 1, and 10) increased prominently in Rab25 KO mice. In line with this, depletion of Rab25 with single hairpin RNA increased the expression of differentiation markers in a human keratinocyte cell line, HaCaT. Transcriptomic analysis of the skin revealed increased expression of genes associated with skin development, epidermal development, and keratinocyte differentiation in Rab25 KO mice. Collectively, these results suggested that Rab25 is involved in the regulation of epidermal differentiation and proliferation.

• International journal of thyroidology
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• v.11 no.2
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• pp.123-129
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• 2018

Background and Objectives: Hypermethylation of the tumor suppressor gene RASSF1A and activating mutation of BRAF gene have been recently reported in thyroid cancers. To investigate the role of these two epigenetic and genetic alterations in thyroid tumor progression, methylation of RASSF1A and BRAF mutation were examined in thyroid tumors. Materials and Methods: During 2007 to 2017, 69 papillary carcinomas, 18 nodular hyperplasia, 3 follicular carcinomas, and 13 follicular adenomas were selected. The methylation-specific polymerase chain reaction (MSP) technique was used in detecting RASSF1A methylation and polymerase chain reaction (PCR)-single-stranded conformation polymorphism and sequencing were used for BRAF gene mutation study. Results: The hypermethylation of the RASSF1A gene was found in 84.6%, 100% and 57.9% of follicular adenomas, follicular carcinomas, and papillary carcinomas, respectively. Nodular hyperplasia showed a hypermethylation in 33.3%. The BRAF mutation at V600E was found in 60.7% of papillary carcinoma and 27.0% of nodular hyperplasia, but none of follicular neoplasms. The BRAF mutation was correlated with the lymph node metastasis and MACIS clinical stage. There is an inverse correlation between RASSF1A methylation and BRAF mutation in thyroid lesions. Conclusion: Epigenetic inactivation of RASSF1A through aberrant methylation is considered to be an early step in thyroid tumorigenesis, and the BRAF mutation plays an important role in the carcinogenesis of papillary carcinoma, providing a genetic marker.