Alternative Splicing of Breast Cancer Associated Gene BRCA1 from Breast Cancer Cell Line

Lixia, Miao,Zhijian, Cao,Chao, Shen,Chaojiang, Gu,Congyi, Zheng Korean Society for Biochemistry and Molecular Biol 2007 Journal of biochemistry and molecular biology Vol.40 No.1

Breast cancer is the most common malignancy among women, and mutations in the BRCA1 gene produce increased susceptibility to these malignancies in certain families. In this study, the forward 1-13 exons of breast cancer associated gene BRCA1 were cloned from breast cancer cell line ZR-75-30 by RT-PCR method. Sequence analysis showed that nine BRCA1 splice forms were isolated and characterized, compared with wild-type BRCA1 gene, five splice forms of which were novel. These splice isoforms were produced from the molecular mechanism of 5' and 3' alternative splicing. All these splice forms deleting exon 11b and the locations of alternative splicing were focused on two parts:one was exons 2 and 3, and the other was exons 9 and 10. These splice forms accorded with GT-AG rule. Most these BRCA1 splice variants still kept the original reading frame. Western blot analysis indicated that some BRCA1 splice variants were expressed in ZR-75-30 cell line at the protein level. In addition, we confirmed the presence of these new transcripts of BRCA1 gene in MDA-MB-435S, K562, Hela, HLA, HIC, H9, Jurkat and human fetus samples by RT-PCR analysis. These results suggested that breast cancer associated gene BRCA1 may have unexpectedly a large number of splice variants. We hypothesized that alternative splicing of BRCA1 possibly plays a major role in the tumorigenesis of breast and/or ovarian cancer. Thus, the identification of cancer-specific splice forms will provide a novel source for the discovery of diagnostic or prognostic biomarkers and tumor antigens suitable as targets for therapeutic intervention.

A Case of MOGAD Complicated With Cerebral Vasculitis: Case Report and Literature Review

Yimin Cao,Jingbo Xu,Zexi Yi,Lixia Zhou 대한신경과학회 2023 Journal of Clinical Neurology Vol.19 No.1

Long Non-Coding RNA CCAT1 Acts as a Competing Endogenous RNA to Regulate Cell Growth and Differentiation in Acute Myeloid Leukemia

Chen, Lianxiang,Wang, Wei,Cao, Lixia,Li, Zhijun,Wang, Xing Korean Society for Molecular and Cellular Biology 2016 Molecules and cells Vol.39 No.4

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.

Efficacy and safety of Gegen Qinlian decoction for normalizing hyperglycemia in diabetic patients: A systematic review and meta-analysis of randomized clinical trials

Ryuk, Jin Ah,Lixia, Mu,Cao, Shihua,Ko, Byoung-Seob,Park, Sunmin Elsevier 2017 COMPLEMENTARY THERAPIES IN MEDICINE Vol.33 No.-

<P><B>Abstract</B></P> <P><B>Objectives</B></P> <P>A systematic review and meta-analysis was conducted to evaluate the efficacy and safety of Gegen Qinlian decoction (GQD) for normalizing hyperglycemia in T2DM patients by pooling all available RCTs.</P> <P><B>Methods</B></P> <P>All relevant RCTs were searched using the keywords: “GQD”, “T2DM”, “hyperglycemia” and “insulin” from the electronic databases including PubMed, EMBASE, Cochrane Library, Korean databases, Chinese medical databases, and Indian scientific database. Each RCT included the control (metformin) and experimental (GQD+metformin) groups. The outcome measures were the assessments of changes in the severity of diabetic symptoms such as “markedly effective” and “effective” (fasting plasma glucose levels: <7 and 7–9, respectively; 2h postprandial glucose levels: <8.3 and 8.3–10.5mmol/L, respectively) after 8 weeks of treatment in each RCT.</P> <P><B>Results</B></P> <P>There were 186 articles selected from the initial searches and 181 irrelevant and duplicate articles were removed. Finally, 5 relevant RCTs involving 499 patients were included in this review. The meta-analysis showed the odds ratio of favorable GQD effect on the marked effectiveness of glycemia (n=499, OR: 2.34, 95% CI: 1.63–3.37, P<0. In a subgroup analysis by GQD composition, 4 RCTs with original GQD composition also showed the odds ratio of the original GQD effect on the marked effectiveness of glycemia (n=339, OR: 2.58; 95% CI=1.65–4.02, P<0.0001) in comparison to the control group. All five studies used an appropriate method for randomization of the subjects but some of them included allocation concealment and blinding of patients and practitioners. There was no significant publication bias in the meta-analysis.</P> <P><B>Conclusion</B></P> <P>The GQD and metformin had a synergistic effect on glycemic control in comparison to metformin alone as a T2DM therapy. More rigorous and larger studies are needed to confirm the therapeutic efficacy of GQD for hyperglycemia due to the moderate to high risk of bias in the 5 RCTs.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Five RCTs including 499 type 2 diabetic patients examined the efficacy of Gegen Qinlian decoction in glycemic control. </LI> <LI> GQD with metformin synergistically enhanced glycemic control in type 2 diabetic patients. </LI> <LI> GQD was not reported any adverse effects. </LI> <LI> More rigorous and larger studies are needed to confirm the therapeutic efficacy of GQD for hyperglycemia. </LI> </UL> </P>

Long Non-Coding RNA CCAT1 Acts as a Competing Endogenous RNA to Regulate Cell Growth and Differentiation in Acute Myeloid Leukemia

Lianxiang Chen,Wei Wang,Lixia Cao,Zhijun Li,Xing Wang 한국분자세포생물학회 2016 Molecules and cells Vol.39 No.4

Long non-coding RNAs (lncRNAs) are involved in multi-ple cellular events, as well as in tumorigenesis. Colon cancer-associated 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. Re-introduction 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.

Effects of Antioxidant Tempol on Systematic Inflammation and Endothelial Apoptosis in Emphysematous Rats Exposed to Intermittent Hypoxia

Haiyan Zhao,Yaping Zhao,Xin Li,Leiqian Xu,Fangxin Jiang,Wanju Hou,Lixia Dong,Jie Cao 연세대학교의과대학 2018 Yonsei medical journal Vol.59 No.9

Purpose: Obstructive sleep apnea and chronic obstructive pulmonary disease are independent risk factors of cardiovascular disease(CVD), and their coexistence is known as overlap syndrome (OS). Endothelial dysfunction is the initial stage of CVD; however,underlying mechanisms linking OS and CVD are not well understood. The aim of this study was to explore whether OS canlead to more severe inflammation and endothelial apoptosis by promoting endothelial dysfunction, and to assess the interventioneffects of antioxidant tempol. Materials and Methods: Male Wistar rats (n=66) were exposed to normal oxygen [normal control (NC) group], intermittent hypoxia(IH group), cigarette smoke (CH group), as well as cigarette smoke and IH (OS group). Tempol intervention was assessed inOS group treated with tempol (OST group) or NaCl (OSN group). After an 8-week challenge, lung tissues, serum, and fresh bloodwere harvested for analysis of endothelial markers and apoptosis. Results: The levels of intracellular adhesion molecule-1, vascular cellular adhesion molecule-1, and apoptosis in circulating epithelialcells were the highest in OS group and the lowest in NC group. These levels were all greater in IH group than in CH group,and were lower in OST group than in OS and OSN groups (all p<0.001). Conclusion: Synergistic effects of IH with cigarette smoke-induced emphysema produce a greater inflammatory status and endothelialapoptosis. OS-related inflammation and endothelial cell apoptosis may play important roles in promoting cardiovasculardysfunction, and antioxidant tempol could achieve a partial protective effect.

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.