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Whasun Lim,Jee-Hye Kim,Suzie E. Ahn,Wooyoung Jeong,Jinyoung Kim,Jae Yong Han,Fuller W. Bazer,Gwonhwa Song 한국동물생명공학회(구 한국동물번식학회) 2011 발생공학 국제심포지엄 및 학술대회 Vol.2011 No.1
Serpins are a superfamily of related protease inhibitors with common structural features and inhibitory mechanisms. However, SERPINA 14 in mammals does not have inhibitory activity against most known proteases. Rather, it may have an immunoregulatory role in mammals to prevent rejection of the fetal allograft by inhibiting lymphocyte proliferation and natural killer cell function. In the pig, SERPINA14 is involved in iron transport to the fetus by binding to and stabilizing the iron-binding protein uteroferrin (ACP5). In chickens, these very little known about serpins in chickens. Therefore, we investigated the expression patterns of serpin genes in the oviduct of adult hens and in the oviduct of 37-day-old chicks treated with an estrogen analogue, diethylstilbestrol (DES). Results indicated that SERPINB3 and SERPINB11 genes were highly expressed in oviducts of DES-treated chicks, but not in oviducts of control chicks. Both SERPINB3 and SERPINB11 transcripts were localized specifically to the gland-like areas of oviducts of DES-treated chicks. Immunohistochemical analyses confirmed that SERPINB3 and SERPINB11 proteins were present in the gland-like area and luminal epithelium of the oviducts of DES-treated chicks. Collectively, the results suggest that SERPINB3 and SERPINB11 are expressed in response to estrogens and they have distinct functions related to development and differentiation of the mature oviduct in hens.
Discovery of prognostic biomarkers for epithelial-derived ovarian cancer
Whasun Lim 한국발생생물학회 2014 한국발생생물학회 학술발표대회 Vol.2014 No.9
Ovarian cancer is the most fetal gynecological malignancy leading cause of cancer-related deaths in women worldwide. Diagnosis of ovarian cancer is hard at an early stage when 90% of patients can be cure due to lack of symptom and early detection markers. Therefore, most of patients with this disease are detected at advanced stage (Stage Ⅲ-Ⅳ) occurring low survival rate (< 30%). More than 90% of ovarian carcinomas are originated from ovarian surface epithelium and it is called as epithelial-derived ovarian cancer (EOC). Recently, previous studies have been showed ovarian cancer could arise from oviduct and oviduct-related genes are up-regulated in hen EOC, the most relevant animal model. Therefore, the objectives of this study were to determine: 1) the distribution and localization of oviduct developmental-regulatory genes including A2M, GAL11, SERPINB3, SERPINB11 and SPP1 in normal and cancerous ovaries of laying hens; 2) the expression pattern of target genes among normal and cancerous ovarian cells of hens and human ovarian cancer cell lines; and 3) the functional role of target gene in human EOC. Results of the present study showed five genes were abundant only in the glandular epithelium of cancerous ovaries of hens. And SERPINB3 was abundant in the nucleus of both chicken and human ovarian cancer cells whereas SERPINB11 was abundant in the cytoplasm. Further, several microRNAs were discovered to influence SERPINB3, GAL11 and SPP1 expression via their 3’-UTR which suggest that post-transcriptional regulation influences target gene expression in chickens. Moreover, in 109 human patients with EOC, 15 (13.8%), 66 (60.6%) and 28 (25.7%) patients showed weak, moderate and strong expression of SERPINB3 protein, respectively. Strong expression of SERPINB3 protein was a prognostic factor for platinum resistance, and for poor progression-free survival. Therefore, oviduct developmental-regulatory genes, especially SERPINB3, may play an important role in ovarian carcinogenesis and be a novel biomarker for predicting platinum resistance and a poor prognosis for survival in patients with EOC.
Exosomes as Therapeutic Vehicles for Cancer
Whasun Lim,Han-Soo Kim 한국조직공학과 재생의학회 2019 조직공학과 재생의학 Vol.16 No.3
BACKGROUND: Exosomes are membrane-enclosed extracellular vesicles implicated in cell–cell communication. Exosomes contain proteins, mRNAs, non-coding RNAs (miRNAs and lncRNAs) and lipids that are derived from producing cells. These nano-sized vesicles are present in biofluids including blood, urine, saliva, amniotic fluid, semen and conditioned media of cultured cells. METHODS: This review summarizes current progress on the strategies of development of diagnostic biomarkers and drug loading onto exosomes for overcoming cancer progression. RESULTS: A number of studies indicate that the exosome appears to be a key player in tissue repair and regeneration of in a number of animal disease models. In addition, alterations of the molecular profiles in exosomes are known to be correlated with the disease progression including cancer, suggesting their usefulness in disease diagnosis and prognosis. Studies utilizing engineered exosomes either by chemical or biological methods have demonstrated promising results in a number of animal models with cancer. CONCLUSION: Understanding the molecular and cellular properties of exosomes offer benefits for cancer diagnosis by liquid biopsy and for their application in therapeutic drug delivery systems. Studies have shown that genetic or molecular engineering of exosomes augmented their target specificity and anticancer activity with less toxicity. Thus, deeper understanding of exosome biology will facilitate their therapeutic potential as an innovative drug delivery system for cancer.
SERPINB3 in the Chicken Model of Epithelial Ovarian Cancer
Whasun Lim,Hee Seung Kim,Jinyoung Kim,Wooyoung Jeong,Jin Young Lee,Chul Hong Lim,Seung Min Bae,Jae Yong Han,Fuller W. Bazer,Gwonhwa Song 한국동물번식학회 2012 Reproductive & Developmental Biology(Supplement) Vol.36 No.2s
SERPINB3 (also known Squamous cell carcinoma antigen 1, SCCA1) is involved in apoptosis, immune response, cell migration and invasiveness of cells. It has been investigated in various types of squamous cell carcinoma. Therefore we investigated the functional role of SERPINB3 gene in human epithelial ovarian cancer (EOC) using laying hens, the most relevant animal model. In 136 laying hens, EOC was found in 10 (7.4%). We compared the expression and localization of SERPINB3 using RT-PCR, quantitative RT-PCR, in situ hybridization and immunohistochemistry, and SERPINB3 activation was detected in chicken and human ovarian cancer cell lines using immunofluorescence microscopy. Thereafter, we examined the prognostic value of SERPINB3 expression in patients with EOC by multivariate linear logistic regression and Cox’ proportional hazard analyses. In present study, SERPINB3 mRNA was induced in cancerous ovaries (p< 0.01), and it was only expressed in the glandular epithelium(GE) of cancerous ovaries of laying hens. SERPINB3 protein was localized predominantly to the nucleus of glandular epithelium in cancerous ovaries of laying hens, and it was abundant in the nucleus of both chicken and human ovarian cancer cell lines. In 109 human patients with EOC, 15 (13.8%), 66 (60.6%) and 28 (25.7%) of those patients showed weak, moderate and strong expression of SERPINB3 protein, respectively. Strong expression of SERPINB3 protein was a prognostic factor for platinum resistance (adjusted OR, 5.94; 95% Confidence Limits, 1.21-29.15). Therefore SERPINB3 may play an important role in ovarian carcinogenesis and be a novel biomarker for predicting platinum resistance and a poor prognosis for survival in patients with EOC. This research was funded by the World Class University (WCU) program (R31-10056), Basic Science Research Program (2010- 0013078) through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology and by the Next-Generation BioGreen 21 Program (No.PJ008142), Rural Development Administration, Republic of Korea.
Wooyoung Jeong,JinyoungKim,SuzieE.Ahn,WhasunLim,Chulhong Lim,Jinyoung Lee,Seungmin Bae,FullerW.Bazer,GwonhwaSong 한국동물번식학회 2012 Reproductive & Developmental Biology(Supplement) Vol.36 No.2s
S-adenosylhomocysteine hydrolase-like protein 1 (AHCYL1), also known as IP3 receptor- binding protein released with IP3 (IRBIT), regulates IP3-induced Ca2+ release in the cytoplasm of cells and, therefore, is likely to be an important gene regulating various biological processes in the oviduct of chickens. However, the identification of the AHCYL1 gene in chickens has not been investigated. Therefore, the objectives of this study were to examine the tissue- and cell-specific expression of AHCYL1 gene in chicken organs, especially in reproductive organ, and determine functional actions of AHCYL1 in chicken oviduct development via estrogen. The results indicated that AHCYL1 mRNA is expressed in chicken reproductive organs and DES(diethylstilbesterol, a synthetic estrogen agonist) stimulates the cell specific expression of AHCYL1 in immature chicken oviduct. These results suggest that AHCYL1 is a novel estrogen-stimulated gene associated with development of the chicken oviduct. Next, in the present study, we show that inhibition of Erk1/2 can block DES-induced AHCYL1 expression. Also, we found that knockdown of AHCYL1 expression down-regulates expression of oviduct specific genes and AHCYL1 expression is regulated at the post-transcriptional level by specific miRNAs. These results strongly suggest that estrogen-mediated AHCYL1 gene expression plays a crucial role in growth, differentiation and function of the hen oviduct. Also, our results will be useful for understanding the fundamental mechanism(s) of estrogen action responsible for development of hen oviduct. This research was funded by the World Class University (WCU) program (R31-10056), Basic Science Research Program (2010-0013078) through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology and by the Next-Generation BioGreen 21 Program (No.PJ008142), Rural Development Administration, Republic of Korea.