MiRNA-206 suppresses PGE2-induced colorectal cancer cell proliferation, migration, and invasion by targetting TM4SF1

Park, Young ,Ran,Seo, Seung ,Young,Kim, Se ,Lim,Zhu, Shi ,Mao,Chun, Sungkun,Oh, Jung-Mi,Lee, Min ,Ro,Kim, Seong ,Hun,Kim, In ,Hee,Lee, Seung ,Ok,Lee, Soo ,Teik,Kim, Portland Press Ltd. 2018 Bioscience reports Vol.38 No.5

<P>MiRNA (miR)-206 plays a tumor suppressor role in various cancer types. Here, we investigated whether miR-206 is involved in prostaglandin E2 (PGE2)-induced epithelial–mesenchymal transition (EMT) in colorectal cancer (CRC) cells through the targetting of transmembrane 4 L six family member 1 (TM4SF1).</P><P>The effect of PGE2 on growth and apoptosis of CRC cells was evaluated using the MTT assay and flow cytometry analysis, respectively. TM4SF1 and miR-206 expression levels were determined with quantitative polymerase chain reaction (qRT-PCR) in CRC tissues and cell lines. The concentration of PGE2 in the serum of CRC patients and healthy controls was measured with an ELISA kit. A miR-206 or TM4SF1 construct was transfected into cells with PGE2. Transwell migration and invasion assays were used to examine cell migration and invasion properties. Additionally, a luciferase assay was performed to determine whether TM4SF1 was directly targetted by miR-206.</P><P>We found that miR-206 was down-regulated and TM4SF1 was up-regulated in human CRC tissues and cell lines. Moreover, miR-206 was negatively correlated with TM4SF1 expression. Bioinformatics analysis and a luciferase reporter assay revealed that miR-206 directly targetted the 3′-untranslated region (UTR) of TM4SF1, and TM4SF1 expression was reduced by miR-206 overexpression at both the mRNA and protein levels. Additionally, PGE2 significantly suppressed the expression of miR-206 and increased the expression of TM4SF1 in CRC cells. PGE2 induction led to enhanced CRC cell proliferation, migration, and invasion. Moreover, the overexpression of miR-206 decreased CRC cell proliferation, migration, and invasion compared with control group in PGE2-induced cells, and these effects could be recovered by the overexpression of TM4SF1. Overexpression of miR-206 also suppressed the expression of β-catenin, VEGF, MMP-9, Snail, and Vimentin and enhanced E-cadherin expression in PGE2-induced cells. These results could be reversed by the overexpression of TM4SF1. At last, up-regulation of miR-206 suppressed expression of <I>p</I>-AKT and <I>p</I>-ERK by targetting TM4SF1 in PGE2-induced cells.</P><P>Our results provide further evidence that miR-206 has a protective effect on PGE2-induced colon carcinogenesis.</P>

La$_{0.875-x}$Yb$_{0.125}$)NbO$_4$:Tm$_x^{3+}$ 형광체의 형광특성

신상수,이성수,박세진,홍창범,신성재,김인기,추장우,홍영범,백민하,최정곤 한국물리학회 2016 새물리 Vol.66 No.10

Tm$^{3+}$and Yb$^{3+}$ co-doped LaNbO$_4$ polycrystalline powders were prepared by using a solid-state reaction method, and their crystallinities and surface morphologies were analyzed by using X-ray diffraction and scanning electron microscopy, respectively. According to the results of X-ray diffraction, the powders showed a polycrystalline monoclinic structure. The photoluminescence and the upconversion luminescence properties of (La$_{0.875-x}$Yb$_{0.125}$)NbO$_4$:Tm$_x^{3+}$($x$ = 0.006, 0.008, 0.01, 0.03 and 0.05) phosphors were investigated in detail. Blue upconversion emissions were observed in the phosphors under excitation by 980 nm laser diode. The powders exhibited strong blue upconversion emission peaks at 476 nm. The maximum emission intensity was obtained for the 0.006 mol Tm$^{3+}$-doped powders, and intensity decreased as the concentration of Tm$^{3+}$ ions was increased to 0.05 mol. 본 연구에서는 Yb$^{3+}$이온의 농도를 0.125 mol에 고정하고 Tm$^{3+}$이온의 농도를 변화시킨(La$_{0.875-x}$Yb$_{0.125}$)NbO$_4$:Tm$_x^{3+}$ ($x$ = 0.006, 0.008, 0.01, 0.03 and 0.05) 형광체 분말을 고상 반응법(solid state reaction)을 이용하여 합성하고 구조적특성 및 표면적특성, 형광특성 을 연구하였다. X-선 회절장치 및 주사전자현미경을 이용하여 형광체 분말의 결정성 및 표면형상을 측정하였으며, 형광광도계를 이용하여 형광특성을 관찰하였고, 980 nm 레이저 다이오드와 분광기를 이용하여 형광체의 상방전환 형광특성을 분석하였다. (La$_{0.875-x}$Yb$_{0.125}$)NbO$_4$:Tm$_x^{3+}$ 분말은 Tm$^{3+}$ 이온의 함유량에 관계없이 단사정계 구조의 다결정상으로 성장함을 알 수 있었다. (La$_{0.875-x}$Yb$_{0.125}$)NbO$_4$:Tm$_x^{3+}$ 분말의 경우 Tm$^{3+}$ 이온의 첨가량이 0.006 mol일 때 형광세가가 가장 강했고, Tm$^{3+}$의 첨가량이 증가할수록 형광의 세기가 감소함을 알 수 있었다.

Transmembrane 4 L six family member 5 (TM4SF5) enhances migration and invasion of hepatocytes for effective metastasis

Lee, Sin‐,Ae,Kim, Tae You,Kwak, Tae Kyoung,Kim, Hyeonjung,Kim, Semi,Lee, Hyo Jeong,Kim, Sung‐,Hoon,Park, Ki Hun,Kim, Hyun Jeong,Cho, Moonjae,Lee, Jung Weon Wiley Subscription Services, Inc., A Wiley Company 2010 Journal of cellular biochemistry Vol.111 No.1

<P><B>Abstract</B></P><P>Overexpression of transmembrane 4 L six family member 5 (TM4SF5), a four‐transmembrane L6 family member, causes aberrant cell proliferation and angiogenesis, but the roles of TM4SF5 in migration, invasion, and tumor metastasis remain unknown. Using in vitro hepatocarcinoma cells that ectopically or endogenously express TM4SF5 and in vivo mouse systems, roles of TM4SF5 in metastatic potentials were examined. We found that TM4SF5 expression facilitated migration, invadopodia formation, MMP activation, invasion, and eventually lung metastasis in nude mice, but suppression of TM4SF5 with its shRNA blocked the effects. Altogether, TM4SF5‐mediated migration and invasion suggest that TM4SF5 may be therapeutically targeted to deal with TM4SF5‐mediated hepatocellular cancers. J. Cell. Biochem. 111: 59–66, 2010. © 2010 Wiley‐Liss, Inc.</P>

TM4SF4 and LRRK2 are Potential Therapeutic Targets in Lung and Breast Cancers through Outlier Analysis

정경수,최준석,구범모,김유진,송지영,성민정,장은솔,노가원,안성빈,이미숙,송경,이한나,김룡남,신영기,오두이,최윤라 대한암학회 2021 Cancer Research and Treatment Vol.53 No.1

Purpose To find biomarkers for disease, there have been constant attempts to investigate the genes that differ from those in the disease groups. However, the values that lie outside the overall pattern of a distribution, the outliers, are frequently excluded in traditional analytical methods as they are considered to be ‘some sort of problem.’ Such outliers may have a biologic role in the disease group. Thus, this study explored new biomarker using outlier analysis, and verified the suitability of therapeutic potential of two genes (TM4SF4 and LRRK2). Materials and Methods Modified Tukey’s fences outlier analysis was carried out to identify new biomarkers using the public gene expression datasets. And we verified the presence of the selected biomarkers in other clinical samples via customized gene expression panels and tissue microarrays. Moreover, a siRNA-based knockdown test was performed to evaluate the impact of the biomarkers on oncogenic phenotypes. Results TM4SF4 in lung cancer and LRRK2 in breast cancer were chosen as candidates among the genes derived from the analysis. TM4SF4 and LRRK2 were overexpressed in the small number of samples with lung cancer (4.20%) and breast cancer (2.42%), respectively. Knockdown of TM4SF4 and LRRK2 suppressed the growth of lung and breast cancer cell lines. The LRRK2 overexpressing cell lines were more sensitive to LRRK2-IN-1 than the LRRK2 under-expressing cell lines. Conclusion Our modified outlier-based analysis method has proved to rescue biomarkers previously missed or unnoticed by traditional analysis showing TM4SF4 and LRRK2 are novel target candidates for lung and breast cancer, respectively.

Bridgman growth, luminescence and energy transfer studies of Tm3+ or/and Dy3+ co-doped Bi4Si3O12 crystal phosphor

Bobo Yang,Jiayue Xu,Jun Zou,Yan Zhang,Tian Tian,Yaoqing Chu,Meiling Wang 한양대학교 세라믹연구소 2016 Journal of Ceramic Processing Research Vol.17 No.6

Tm3+, Dy3+ and Tm3+/Dy3+ co-doped bismuth silicate (Bi4Si3O12, BSO) crystals were successfully grown by the modified verticalBridgeman method. The crystals have about 80% transmittance in the range from 320 nm to 650 nm except several obviouscharacteristic absorption peaks corresponding to transitions of 4f electrons of Tm3+ and Dy3+. The luminescence properties forwhite light emitting diode (w-LED) were investigated. Energy transfer from the Bi3+ ions to the Tm3+ and Dy3+ ions in Tm3+or/and Dy3+ co-doped Bi4Si3O12 crystal has been established by photoluminescence investigation upon UV excitation. Whenexcited by a proper UV-light, Tm3+ doped BSO crystal shows blue emission band centered at 460 nm ascribed to Tm3+ (1D2→ 3F4), Dy3+ doped BSO crystal shows blue band at 480 nm (4F9/2→ 6H15/2), yellow band at 574 nm (4F9/2→ 6H13/2) and red bandat 662 nm (4F9/2→ 6H11/2) of Dy3+ ions. A white light with chromaticity coordinate of x = 0.3298, y = 0.2905 by excitation of357 nm is achieved from Tm3+/Dy3+ co-doped Bi4Si3O12 crystal. These results indicate that Tm3+/Dy3+ co-doped Bi4Si3O12 as awhite emitting crystal has a potential application in white-LED.

PEL-FREEZ DR4 TEST-SSP UNITRAY^TM를 이용한 HLA-DR 검사

최수진,원진연,오흥범 대한임상검사정도관리학회 1999 臨床檢査와 精度管理 Vol.21 No.1

Invited Mini Review : TM4SF5-mediated protein-protein networks and tumorigenic roles

( Jung Weon Lee ) 생화학분자생물학회 2014 BMB Reports Vol.47 No.9

Transmembrane 4 L six family member 5 (TM4SF5), as a membrane glycoprotein with 4 transmembrane domains, issimilar to the tetraspanins in terms of membrane topology and plays important roles in tumorigenesis and tumor metastasis. Especially, TM4SF5 appears to form a massive protein-proteincomplex consisting of diverse membrane proteins and/orreceptors in addition to cytosolic signaling molecules to regulate their signaling activities during the pathological processes. TM4SF5 is shown to interact with integrins α2, α5, and β1, EGFR, IL6R, CD151, focal adhesion kinase (FAK), andc-Src. This review focuses on the significance of the interactions with regards to TM4SF5-positive tumorigenesis and metastasis.

BMB Reports : Therapeutic effect of a TM4SF5-specific peptide vaccine against colon cancer in a mouse model

( Sanghoon Kwon ),( Young Eun Kim ),( Jeong A Park ),( Doo Sik Kim ),( Hyung Joo Kwon ),( Younghee Lee ) 생화학분자생물학회 2014 BMB Reports Vol.47 No.4

Molecular-targeted therapy has gained attention because of its high efficacy and weak side effects. Previously, we confirmed that transmembrane 4 superfamily member 5 protein (TM4SF5) can serve as a molecular target to prevent or treat hepatocellular carcinoma (HCC). We recently extended the application of the peptide vaccine, composed of CpG-DNA, liposome complex, and TM4SF5 peptide, to prevent colon cancer in a mouse model. Here, we first implanted mice with mouse colon cancer cells and then checked therapeutic effects of the vaccine against tumor growth. Immunization with the peptide vaccine resulted in robust production of TM4SF5-specific antibodies, alleviated tumor growth, and reduced survival rate of the tumor-bearing mice. We also found that serum levels of VEGF were markedly reduced in the mice immunized with the peptide vaccine. Therefore, we suggest that the TM4SF5-specific peptide vaccine has a therapeutic effect against colon cancer in a mouse model. [BMB Reports 2014; 47(4): 215-220]

Structural and Kinetic Characteristics of 1,4-Dioxane-Degrading Bacterial Consortia Containing the Phylum TM7

( Ji-hyun Nam ),( Jey-r S. Ventura ),( Ick Tae Yeom ),( Yongwoo Lee ),( Deokjin Jahng ) 한국미생물 · 생명공학회 2016 Journal of microbiology and biotechnology Vol.26 No.11

1,4-Dioxane-degrading bacterial consortia were enriched from forest soil (FS) and activated sludge (AS) using a defined medium containing 1,4-dioxane as the sole carbon source. These two enrichments cultures appeared to have inducible tetrahydrofuran/dioxane and propane degradation enzymes. According to qPCR results on the 16S rRNA and soluble di-iron monooxygenase genes, the relative abundances of 1,4-dioxane-degrading bacteria to total bacteria in FS and AS were 29.4% and 57.8%, respectively. For FS, the cell growth yields (Y), maximum specific degradation rate (V_max), and half-saturation concentration (K_m) were 0.58 mg-protein/mg-dioxane, 0.037 mg-dioxane/mg-protein·h, and 93.9 mg/l, respectively. For AS, Y, V_max, and K_m were 0.34 mg-protein/mg-dioxane, 0.078 mg-dioxane/mg-protein·h, and 181.3 mg/l, respectively. These kinetics data of FS and AS were similar to previously reported values. Based on bacterial community analysis on 16S rRNA gene sequences of the two enrichment cultures, the FS consortium was identified to contain 38.3% of Mycobacterium and 10.6% of Afipia, similar to previously reported literature. Meanwhile, 49.5% of the AS consortium belonged to the candidate division TM7, which has never been reported to be involved in 1,4-dioxane biodegradation. However, recent studies suggested that TM7 bacteria were associated with degradation of non-biodegradable and hazardous materials. Therefore, our results showed that previously unknown 1,4-dioxane-degrading bacteria might play an important role in enriched AS. Although the metabolic capability and ecophysiological significance of the predominant TM7 bacteria in AS enrichment culture remain unclear, our data reveal hidden characteristics of the TM7 phylum and provide a perspective for studying this previously uncultured phylotype.

우고닌(Wogonin)이 poly I:C로 유발된 TM4세포 내 하이드로겐퍼록사이드 생성에 미치는 영향

박완수 ( Wansu Park ) 대한본초학회 2021 大韓本草學會誌 Vol.36 No.5

Objectives : The aim of this study is to investigate the effect of wogonin on the production of hydrogen peroxide in polyinosinic:polycytidylic acid (poly I:C)-stimulated TM4 mouse sertoli cells. Methods : TM4 were treated with poly I:C (50 ug/mL) and wogonin at concentrations of 5, 10, 25, and 50 μM for 30 min, 2 hr, 12 hr, 18 hr, and 24 hr. The production of intracellular hydrogen peroxide was measured by dihydrorhodamine 123 assay. Results : For 30 min, 2 hr, 12 hr, 18 hr, and 24 hr treatment, wogonin significantly inhibited intracellular hydrogen peroxide productions of TM4 at the concentration of 5, 10, 25, and 50 μM (p <0.05). In details, production of hydrogen peroxide in poly I:C-stimulated TM4 treated for 30 min with wogonin at concentrations of 5, 10, 25, and 50 μM was 95.67%, 92.69%, 92.05%, and 91.97% of the control group treated with poly I:C only, respectively; the production of hydrogen peroxide for 2 hr was 94.44%, 94.41%, 93%, and 92.98%, respectively; production of hydrogen peroxide for 12 hr was 96.78%, 95.32%, 94.33%, and 93.17%, respectively; production of hydrogen peroxide for 18 hr was 94.7%, 93.4%, 93.38%, and 93.35%, respectively; and production of hydrogen peroxide for 24 hr was 95.75%, 94.77%, 94.58%, and 92.8%, respectively. Conclusions : Wogonin might have anti-viral property related with its inhibition of intracellular hydrogen peroxide production in poly I:C-stimulated TM4 cells.