Differential Expression of SERPINs in the Chicken Oviduct

Whasun Lim(임화선),Jihye Kim,Suzie E. Ahn,Wooyoung Jeong,Jinyoung Kim,Jin Won Choi,Jae Yong Han,Fuller W. Bazer,Gwonhwa Song 한국가금학회 2010 한국가금학회 정기총회 및 학술발표회 Vol.27 No.-

Serpins are a superfamily of relating to inhibit protease with common structural features and inhibitory mechanisms. It is also known as ov-serpins in chicken which are ovalbumin and secreted chicken oviduct protein. However, to our knowledge, it is relatively little known about serpins in chickens. In this study, we investigated the expression patterns of serpin genes in the adult chicken oviduct and also the neonatal oviduct of 37-day-old chicks which were treated with an estrogen analogue, diethylstilbestrol (DES). As results SERPINB3 and SERPINB11 genes were highly expressed in DES-treated oviducts but not in non-treated oviduct. Localization of SERPINB3 and SERPINB11 transcripts were specifically found in the gland-like area of adult chicken oviduct. Collectively, our current data suggest that SERPINB3 and SERPINB11 may have distinct functions in the differentiation processes dependent of steroid hormone regulation in the hen oviduct.

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.

Inhibitory effects of delphinidin on the proliferation of ovarian cancer cells via PI3K/AKT and ERK 1/2 MAPK signal transduction

Lim, Whasun,Song, Gwonhwa D.A. Spandidos 2017 Oncology letters Vol.14 No.1

<P>Delphinidin is a member of the anthocyanidin family and is a natural pigment in red cabbage, berries, sweet potatoes and grapes. It possesses nutraceutical properties against various chronic diseases and types of cancer. However, little is known about its preventative effects on epithelial ovarian cancer, a disease that is associated with a low survival rate, a poor prognosis and a high rate of recurrence. The results of the present study demonstrated that the proliferation of SKOV3 cells decreased in a dose-dependent manner in response to treatment with delphinidin, and the phosphorylation of carcinogenic protein kinases associated with the progression of epithelial ovarian cancer was affected by delphinidin treatment. The levels of phosphorylated protein kinase B (AKT), ribosomal protein S6 kinase β-1 (P70S6K), ribosomal protein S (S6), extracellular signal-regulated kinase (ERK)1/2 and p38 were suppressed by increasing concentrations of delphinidin. Furthermore, the combination of certain pharmacological inhibitors, including phosphoinositide 3-kinase (PI3K; LY294002), ERK1/2 (U0126) and delphinidin significantly reduced the proliferation of SKOV3 cells and the phosphorylation of each of those target proteins. In addition, delphinidin treatment exerted anti-proliferative effects on paclitaxel-resistant SKOV3 cells, compared with treatment with paclitaxel alone. These results indicate that delphinidin inhibits the proliferation of SKOV3 cells through inactivation of PI3K/AKT and ERK1/2 mitogen-activated protein kinase signaling cascades, and that this cell signaling pathway may be a pivotal therapeutic target for the prevention of epithelial ovarian cancer, including paclitaxel-resistant ovarian cancer.</P>

Differential Expression of Gallicin 11 in the Oviduct in Response to Diethylstilbestrol and in Ovarian Carcinomas of Chickens

Whasun Lim,Wooyoung Jeong,Seung-Min Bae,Gahee Jo,Gwonhwa Song 한국동물생명공학회(구 한국동물번식학회) 2013 발생공학 국제심포지엄 및 학술대회 Vol.2013 No.1

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.

Functional Role of Polyphenols in Reproductive Health and Early Pregnancy

Whasun Lim,Gwonhwa Song 한국식품영양과학회 2016 한국식품영양과학회 학술대회발표집 Vol.2016 No.10

Differential expression of select members of the SLC family of genes and regulation of expression by microRNAs in the chicken oviduct.

Lim, Chul-Hong,Jeong, Wooyoung,Lim, Whasun,Kim, Jinyoung,Song, Gwonhwa,Bazer, Fuller W Society for the Study of Reproduction [etc.] 2012 BIOLOGY OF REPRODUCTION Vol.87 No.6

<P>The yolk and white of eggs from chickens contain proteins and other molecules either secreted or transported by cells of the reproductive tract, or secreted by the liver and transported to the ovarian follicles of laying hens. Nutrients transported by solute carriers (SLCs) include glucose, electrolytes, and amino acids. Although SLC genes have been investigated in mammals, there are few studies of expression of SLC genes in the chicken oviduct. Therefore, we investigated temporal and cell-specific expression of selected SLC genes at 3 h and 20 h postovulation and regulation of their expression by microRNAs (miRs). Expression of SLC1A4 (glutamate and neutral amino acid transporter), SLC13A2 (dicarboxylate transporter), and SLC35B4 (UDP-xylose: UDP-N-acetylglucosamine transporter) mRNAs was limited to glandular epithelium (GE), while SLC4A5 (sodium bicarbonate cotransporter) and SLC7A3 (cationic amino acid transporter) mRNAs were expressed predominantly in the luminal epithelium of the magnum. Interestingly, SLC1A4, SLC4A5, SLC13A2 and SLC35B4 mRNAs were abundant only in GE of the shell gland, whereas SLC7A3 was not detected in the shell gland. In the magnum, SLC7A3 and SLC4A5 were expressed, but SLC1A4, SLC35B4, and SLC13A2 were not expressed at 20 h postovulation. In the shell gland, all SLC mRNAs were expressed at both time points, except for SLC7A3. The miRNA target validation assay revealed that miR-1764 and miR-1700 bind directly to SLC13A2 and SLC35B4 transcripts, respectively, to regulate expression. Results of this study demonstrate cell-specific and temporal changes in expression of selected SLC genes and regulation of SLC13A2 and SLC35B4 expression by miRs in the oviduct of laying hens.</P>

Chicken SERPINBs: Characteristics, Tissue Specific Expression and Regulation of Expression by Estrogen

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.

Coumestrol induces mitochondrial dysfunction by stimulating ROS production and calcium ion influx into mitochondria in human placental choriocarcinoma cells

Lim, Whasun,Yang, Changwon,Jeong, Muhah,Bazer, Fuller W,Song, Gwonhwa Oxford University Press 2017 Molecular human reproduction Vol.23 No.11

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.