MUC16 facilitates cervical cancer progression via JAK2/STAT3 phosphorylation‑mediated cyclooxygenase‑2 expression

Hui Shen,Meng Guo,Lu Wang,Xinyue Cui 한국유전학회 2020 Genes & Genomics Vol.42 No.2

Objectives MUC16 (mucin 16, also known as CA-125, cancer antigen 125, carcinoma antigen 125, or carbohydrate antigen 125) has been predicted as tumor biomarker for therapy. We determined to investigate effects and regulatory mechanism of MUC16 on cervical tumorigenesis. Methods Expression levels of MUC16 in cervical cancer cell lines was analyzed via qRT-PCR (quantitative real-time polymerase chain reaction). Knockdown of MUC16 was conducted via shRNA (Short hairpin RNA) transfection. MTT and colony formation assays were used to investigate effect of MUC16 on cell proliferation. Wound healing assay was utilized to detect migration and transwell assay to detect invasion. The underlying mechanism was demonstrated via western blot analysis. Results MUC16 was elevated in cervical cancer cell lines. MUC16 knockdown inhibited cell proliferation, invasion and migration. Gain- and loss-of functional assays revealed that over-expression of MUC16 activated Janus Kinase 2 (JAK2)/ signal transducer and activator of transcription 3 (STAT3) via phosphorylation, thus facilitating cyclooxygenase-2 (COX-2) expression, while knockdown of MUC16 demonstrated the reverse effect on JAK2/STAT3 activation and COX-2 expression. Moreover, inhibition of JAK2/STAT3 attenuated the regulation of MUC16 on COX-2. Conclusions MUC16 enhanced proliferation and invasion of cervical cancer cells via JAK2/STAT3 phosphorylation-mediated cyclooxygenase-2 expression, suggesting the potential therapeutic target ability of MUC16 to treat cervical cancer.

Tajik Father and Daughter

Shen Lu 한국디자인학회 2018 한국디자인학회 국제초대전도록 Vol.2018 No.11

Weight Loss Correlates with Macrophage Inhibitory Cytokine-1 Expression and Might Influence Outcome in Patients with Advanced Esophageal Squamous Cell Carcinoma

Lu, Zhi-Hao,Yang, Li,Yu, Jing-Wei,Lu, Ming,Li, Jian,Zhou, Jun,Wang, Xi-Cheng,Gong, Ji-Fang,Gao, Jing,Zhang, Xiao-Tian,Li, Jie,Li, Yan,Shen, Lin Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.15

Background: Weight loss during chemotherapy has not been exclusively investigated. Macrophage inhibitory cytokine-1 (MIC-1) might play a role in its etiology. Here, we investigated the prognostic value of weight loss before chemotherapy and its relationship with MIC-1 concentration and its occurrence during chemotherapy in patients with advanced esophageal squamous cell carcinoma (ESCC). Materials and Methods: We analyzed 157 inoperable locally advanced or metastatic ESCC patients receiving first-line chemotherapy. Serum MIC-1 concentrations were assessed before chemotherapy. Patients were assigned into two groups according to their weight loss before or during chemotherapy:>5% weight loss group and ${\leq}5%$ weight loss group. Results: Patients with weight loss>5% before chemotherapy had shorter progression-free survival period (5.8 months vs. 8.7 months; p=0.027) and overall survival (10.8 months vs. 20.0 months; p=0.010). Patients with weight loss >5% during chemotherapy tended to have shorter progression-free survival (6.0 months vs. 8.1 months; p=0.062) and overall survival (8.6 months vs. 18.0 months; p=0.022), and if weight loss was reversed during chemotherapy, survival rates improved. Furthermore, serum MIC-1 concentration was closely related to weight loss before chemotherapy (p=0.001) Conclusions: Weight loss both before and during chemotherapy predicted poor outcome in advanced ESCC patients, and MIC-1 might be involved in the development of weight loss in such patients.

The type II histidine triad protein HtpsC facilitates invasion of epithelial cells by highly virulent Streptococcus suis serotype 2

Lu Yunjun,Li Shu,Shen Xiaodong,Zhao Yan,Zhou Dongming,Hu Dan,Cai Xushen,Lu Lixia,Xiong Xiaohui,Li Ming,Cao Min 한국미생물학회 2021 The journal of microbiology Vol.59 No.10

Streptococcus suis serotype 2 (S. suis 2) is an important zoonotic pathogen that presents a significant threat both to pigs and to workers in the pork industry. The initial steps of S. suis 2 pathogenesis are unclear. In this study, we found that the type II histidine triad protein HtpsC from the highly virulent Chinese isolate 05ZYH33 is structurally similar to internalin A (InlA) from Listeria monocytogenes, which plays an important role in mediating listerial invasion of epithelial cells. To determine if HtpsC and InlA function similarly, an isogenic htpsC mutant (ΔhtpsC) was generated in S. suis by homologous recombination. The htpsC deletion strain exhibited a diminished ability to adhere to and invade epithelial cells from different sources. Double immunofluorescence microscopy also revealed reduced survival of the ΔhtpsC mutant after cocultivation with epithelium. Adhesion to epithelium and invasion by the wild type strain was inhibited by a monoclonal antibody against E-cadherin. In contrast, the htpsC-deficient mutant was unaffected by the same treatment, suggesting that E-cadherin is the host-cell receptor that interacts with HtpsC and facilitates bacterial internalization. Based on these results, we propose that HtpsC is involved in the process by which S. suis 2 penetrates host epithelial cells, and that this protein is an important virulence factor associated with cell adhesion and invasion.

Glutathione Concentration as Affected by Sulfate Supply Level and its Relationship with Sulfate Uptake and Assimilatory Enzymes Activity in Rape Plants

Lu-Shen Li(이노신),Tae-Hwan Kim(김태환) 한국초지조사료학회 2011 한국초지조사료학회지 Vol.31 No.1

유채 (Brassica napus L.)에서 황 공급수준에 따른 글루타치온 함량의 변화가 황 흡수 및 동화관련 효소 활력에 미치는 영향을 규명하고자, SO₄²? 농도를 4수준 (0, 0.1, 1.0 및 2.0 mM)으로 25시간 처리한 후 식물조직 내 글루타치온 함량을 측정하고, SO₄²? 흡수, ATP sulfurylase (ATPS) 및 Oacteylserine (thiol) lyase (OASTL) 효소 활력과의 상관관계를 분석하였다. SO₄²? 흡수는 황 공급수준에 따라 평행적인 증가를 보였으나 잎과 뿌리 조직의 단백질 함량은 유의적인 차이가 없었다. ATPS 활력은 황 공급수준이 0 mM에서 2.0 mM로 증가함에 따라 유의적으로 감소 (p<0.05) 하였으며, OASTL 활력은 황 결핍수준인 0 및 0.1 mM에서만 유의적인 감소 (p<0.05)를 보였다. 어린잎, 중간잎 및 뿌리 조직에서는 황 결핍수준이 증가함에 따라 글루타치온 함량은 유의적으로 증가 (p<0.05) 하였으나, 뿌리에서는 처리간 유의적인 차이가 없었다. 황 공급수준의 감소에 따른 글루타치온 함량과 SO₄²? 흡수 간에는 고도의 정의 상관관계 (p<0.01)가 인정되었으며, 잎과 뿌리내의 ATPS 및 잎조직의 OASTL 효소활력 간에는 각각 부의 상관관계 (p<0.05)가 인정되었다. The glutathione (GSH) concentration in leaves of different maturities and roots of forage rape (Brassica napus L.) supplied with four levels of external SO₄²? (0, 0.1, 1.0 and 2.0 mM) supply were measured. The relationships of GSH concentration with SO₄²? uptake, ATP sulfurylase (ATPS) and O-acteylserine (thiol) lyase (OASTL) activity were also assessed. The SO₄²? uptake increased in parallel with the external SO₄²? supply, while protein concentration was not significantly changed. The ATPS activity increased continuously with decreasing SO₄²? supply from 2.0 to 0 mM, while the OASTL activity decreased significantly only at S-deficient conditions (0 and 0.1 mM). The GSH concentration in the young leaves, middle leaves and roots continuously increased (except for between 1.0 and 2.0 mM in the middle leaves and roots) as the external S supply was increased, but no significant changes occurred in the old leaves. The increased endogenous GSH concentration, affected by the SO₄²? supply level, was significantly related with the decrease in ATPS activity in both leaves and roots, and the decrease in OASTL activity only in leaves..

Sulfur Deficiency Effects on Nitrate Uptake and Assimilatory Enzyme Activities in Rape Plants

Lu-Shen Li(이노신),Yu-Lan Jin(김옥란),Bok-Rye Lee(이복례),Tae-Hwan Kim(김태환) 한국초지조사료학회 2009 한국초지조사료학회지 Vol.29 No.2

유채 (Brassica napus L.)에서 황 결핍이 NO₃⁻ 흡수와 동화에 대한 영향을 알아보고자 SO₄²⁻ 농도를 세가지 수준 (1 mM SO₄²⁻, 대조구; 0.1 mM SO₄²⁻, 결핍; 0 mM SO₄²⁻, 무공급)으로 25시간 처리한 후 NO₃⁻ 흡수량, 식물조직내의 nitrate reductase (NR) 및 glutamine syntheetase (GS) 활성을 분석하였다. 25시간 처리과정에서 황결핍 조건하에서의 NO₃⁻의 흡수는 대조구와 큰 차이를 나타내지 않은 반면, 황 무공급구에서는 NO₃⁻의 흡수는 유의적으로 감소하였다. NR 활성은 잎과 뿌리 조직에서 공히 SO₄²⁻ 농도가 감소됨에 따라 감소하였다. 특히 어린잎과 중간 잎의 황 결핍 처리구에서 각각 35% 및 황 무공급구에서 70%의 뚜렸한 감소를 보였다. 뿌리에서는 오직 황 무공급구에서 유의적인 감소(-29%)를 보였다. SO₄²⁻ 농도에 따른 잎 조직에서 GS 활성은 잎의 성숙 정도에 따라 차이를 보였으며, 전반적으로 황 결핍과 황 무공급구에서 감소하는 경향을 보였다. 뿌리조직에서 GS 활성은 황 무공급구에서만 유의적인 감소를 보였다. 이러한 결과들은 황 공급이 제한을 받는 조건에서 질산염의 흡수가 감소되며, 식물조직체내의 질산염환원과 아미노산 합성관련 효소의 활성이 제한을 받았다는 것을 보여준다.

Research on Industry Competition, Ownership Structure and Earnings Management : Empirical Analysis based on Listed Bank

Lu Shen 보안공학연구지원센터 2016 International Journal of Smart Home Vol.10 No.3

Earnings management is an important strategic decision of banks, which will affect the future development direction of the bank. In this paper, author selects the data of listed banking industry in China from 2004 as the sample, and tries to find out the factors that affect the earnings management, especially the influence of the ownership structure and the competition on earnings management. Through the empirical analysis, we found that the proportion of the first largest shareholder and the degree of earnings management of the bank presents the "U" type nonlinear relationship; the proportion of the senior executives has negative impact on the earnings management. There is a positive correlation between the market share competition and earnings management in the banking industry. Overall, the rise in the absolute amount or relative amount of bank loans will increase the level of earnings management of banks. The degree of competition of state-owned banks is negatively related to earnings management, but non state-owned banks were positively correlated to earnings management.

Sulfur Deficiency Effects on Sulfate Uptake and Assimilatory Enzymes Activity in Rape Plants

Lu-Shen Li(이노신),Yu-Lan Jin(김옥란),Bok-Rye Lee(이복례),Tae-Hwan Kim(김태환) 한국초지조사료학회 2009 한국초지조사료학회지 Vol.29 No.2

유채 (Brassica napus L.)에서 외생적 황 공급이 SO₄²⁻ 흡수와 동화에 대한 영향을 알아보고자 SO₄²⁻ 농도를 세가지 수준 (1 mM SO₄²⁻, 대조구; 0.1 mM SO₄²⁻, 결핍; 0 mM SO₄²⁻, 무공급)으로 25시간 처리한 후 식물조직내에서의 SO₄²⁻ 농도, ATP sulfurylase와 APS reductase 활성을 측정하였다. SO₄²⁻의 흡수와 식물조직내에서의 SO₄²⁻의 농도는 결핍과 무공급 조건하에서 현저하게 감소하였다. ATP sulfurylase 활성은 외부 황 공급의 감소에 따라 증가한 반면, APS reductase 활성은 감소하였다. 황 무공급에 따른 이 두 효소 활력의 유의적인 차이는 어린잎과 중간잎에서만 고찰되었다. 이러한 결과는 한정된 황 조건하에서 특히 어린잎에서 SO₄²⁻ 동화는 더욱 민감하게 반응한다는 것을 제시한다.

Changes in Activity of Key Enzymes related with N and S Assimilation in Response to S-Availability in Rape (Brassica napus L.)

Lu-Shen Li,Sang-Hyun Park,An-Na Cho,Tae-Hwan Kim 한국초지조사료학회 2009 한국초지조사료학회 학술대회논문집 Vol.2009 No.08

To investigate the effect of S-availability on N and S assimilations, Enzymatic activity of nitrate reductase (NR), glutamine synthetase (GS), ATP sulfurylase (ATPS) and O-acetylserine(thiol)lyase (OASTL) was measured, and also followed by their activity staining in forage rape (Brassica napus L.) fed with three different SO₄²? levels (0, 0.1 and 2.0 mM) for 25 hours. NR activity decreased as S-availability decreased, especially in young and middle leaves. S-limited conditions (0 and 0.1 mM sot) resulted in a reduction of GS activity. The activity of ATPS tended to increase with decreasing the exogenous SO₄²? supplying level. The activity of OASTL also increased as S-availability decreased for all leaf tissues, while tended to decrease in root. The results indicated t㏊t N assimilation was restricted by the limited S-nutrition especially in the developing leaf tissues, but S assimilation was stimulated except for OASTL activity in the roots.

Concomitance of P-gp/LRP Expression with EGFR Mutations in Exons 19 and 21 in Non-Small Cell Lung Cancers

Shen Lu,Hong Wei,Weipeng Lu,Mei Li,Qiuping Zhang 연세대학교의과대학 2016 Yonsei medical journal Vol.57 No.1

Purpose: Traditional chemotherapy is the main adjuvant therapy for the treatment of non-small cell lung cancer (NSCLC). However,the emergence of multi-drug resistance (MDR) has greatly restricted the curative effect of chemotherapy. Therefore, it isnecessary to find a method to treat MDR NSCLC clinically. It is worth investigating whether NSCLCs that are resistant to traditionalchemotherapy can be effectively treated with tyrosine kinase inhibitors targeting epidermal growth factor receptor (EGFR). Materials and Methods: The expression of P-glycoprotein (P-gp) and lung resistance-related protein (LRP) was detected by immunohistochemistry,and mutations in EGFR (exons 19 and 21) and Kirsten rat sarcoma viral oncogene homolog (KRAS) (exon 2)were detected by high-resolution melting analysis (HRMA) of surgical NSCLC specimens from 127 patients who did not undergotraditional chemotherapy or radiotherapy. A Pearson chi-square test was performed to analyze the correlations between the expressionof P-gp and LRP and mutations in EGFR and KRAS. Results: The expression frequencies of P-gp and LRP were significantly higher in adenocarcinomas from non-smoking patients;the expression frequency of LRP was significantly higher in cancer tissue from female patients. The frequency of EGFR mutationswas significantly higher in well to moderately differentiated adenocarcinomas from non-smoking female patients. The frequencyof EGFR mutations in the cancers that expressed P-gp, LRP, or both P-gp and LRP was significantly higher than that in cancersthat did not express P-gp or LRP. Conclusion: NSCLCs expressing P-gp/LRP bear the EGFR mutation in exon 19 or 21 easily.