scholarly journals Effect of NIMA-related kinase 2B on the sensitivity of breast cancer to paclitaxel in vitro and vivo

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831769975 ◽  
Author(s):  
Yahong Wang ◽  
Honghong Shen ◽  
Quangui Yin ◽  
Tongxian Zhang ◽  
Ziyu Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Nude Mouse ◽  
Messenger Rna ◽  
Small Interfering Rna ◽  
Ductal Carcinoma ◽  
Positive Lymph Node ◽  
Disease Rates ◽  
Interfering Rna ◽  
Inhibit Cell Proliferation

NIMA-related kinase 2B has been known to be an important centrosome regulatory factor. The aim of this study was to investigate the effect of NIMA-related kinase 2B on the sensitivity of breast cancer to paclitaxel. We detected the expression of NIMA-related kinase 2B messenger RNA in MCF-10 cells, including MCF-10A, MCF-10AT, MCF-10DCIS.com , and MCF-10CA1a. The influence of NIMA-related kinase 2B in nude mouse was also detected. The association between NIMA-related kinase 2B and clinicopathological factors was explored in invasive ductal carcinoma tissues. NIMA-related kinase 2B was lowly expressed in the precancerous cells, MCF-10A and MCF-10AT, and it was highly expressed in carcinomatous cells, MCF-10DCIS.com and MCF-10CA1a. The upregulation of NIMA-related kinase 2B can introduce the growth of MCF-10AT cells, knockdown of NIMA-related kinase 2B could remarkably inhibit cell proliferation in MCF-10DCIS.com and MCF-10 CA1a cells. Comparing the volume of the xenografts in nude mouse, we found that the tumors treated by NIMA-related kinase 2B small interfering RNA associated with paclitaxel were the smallest among all the groups. Expression of NIMA-related kinase 2B messenger RNA was associated with higher histological grades, positive lymph node, and high Ki67 index (>20%). The partial response rates were 75.0% in NIMA-related kinase 2B negative (NIMA-related kinase 2B−) patients and 15.8% in NIMA-related kinase 2B++ patients. The progressive disease rates were 10.0% in NIMA-related kinase 2B− patients and 52.6% in NIMA-related kinase 2B++ patients ( p = 0.002). Our findings suggested that NIMA-related kinase 2B could play a role in the development and progression of breast cancer. Combination treatment using NIMA-related kinase 2B small interfering RNA and paclitaxel might be a novel potential therapy method for breast cancer.

scholarly journals Effect of SOCS1 silencing on proliferation and apoptosis of melanoma cells: An in vivo and in vitro study

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831769431
Author(s):  
Sheng-Jia Yu ◽  
Zi-Wen Long
Keyword(s):  
Messenger Rna ◽  
Small Interfering Rna ◽  
Melanoma Cells ◽  
Janus Kinase ◽  
Extracellular Signal ◽  
Proliferation And Apoptosis ◽  
Protein Expressions ◽  
Interfering Rna

This study aimed to investigate the effect of SOCS1 silencing on the proliferation and apoptosis of melanoma cells by in vivo and in vitro studies. Immunohistochemical staining was used to detect SOCS1 expression in melanoma tissues and pigmented nevi. Quantitative real-time polymerase chain reaction and western blotting were applied to detect the messenger RNA and protein expressions of SOCS1 in primary human melanocytes and malignant melanoma cell lines (A375, SK-MEL-5, M14, and MV3). Melanoma cells were assigned into mock, negative small interfering RNA, and SOCS1-small interfering RNA groups. The proliferation, cell cycle and apoptosis, and messenger RNA expression of SOCS1 in MV3 and A375 cells were detected using MTT assay, flow cytometry, and quantitative real-time polymerase chain reaction, respectively. The expressions of SOCS1 protein, extracellular signal–regulated kinase, and janus kinase signal transduction and activators of transcription signaling pathways–related proteins were detected using western blotting. After the establishment of subcutaneous xenograft tumor models in nude mice, the latent period, size, volume and growth speed of xenograft tumors in the mock, negative small interfering RNA, and SOCS1-small interfering RNA groups were examined and compared. The results indicated that positive expression rate of SOCS1 was higher in malignant melanoma tissues than in pigmented nevi. MV3 cells had the highest messenger RNA and protein expressions of SOCS1, followed by A357 cells. Compared with the mock and negative small interfering RNA groups, SOCS1-small interfering RNA group showed lower cell viability, elevated cell apoptosis, more cells in G0/G1 phase and less cells in S and G2/M phases, and decreased messenger RNA and protein expressions of SOCS1, p-ERK1/2, p-JAK2, p-STAT1, and p-STAT3. Compared with the mock and negative small interfering RNA groups, the SOCS1-small interfering RNA group showed longer latent period of tumor, smaller tumor size and volume, and smoother tumor growth curve. To conclude, SOCS1 silencing can inhibit proliferation and induce apoptosis of MV3 and A357 melanoma cells in vivo and in vitro by inhibiting extracellular signal–regulated kinase and janus kinase signal transduction and activators of transcription signaling pathways.

scholarly journals Muscle-specific microRNA miR-206 promotes muscle differentiation

2006 ◽  
Vol 174 (5) ◽  
pp. 677-687 ◽  
Author(s):  
Hak Kyun Kim ◽  
Yong Sun Lee ◽  
Umasundari Sivaprasad ◽  
Ankit Malhotra ◽  
Anindya Dutta
Keyword(s):  
Antisense Oligonucleotide ◽  
Small Interfering Rna ◽  
Degradation Process ◽  
Microrna Target ◽  
C2c12 Myoblasts ◽  
Target Sites ◽  
The Many ◽  
Interfering Rna ◽  
In Vitro Transfection

Three muscle-specific microRNAs, miR-206, -1, and -133, are induced during differentiation of C2C12 myoblasts in vitro. Transfection of miR-206 promotes differentiation despite the presence of serum, whereas inhibition of the microRNA by antisense oligonucleotide inhibits cell cycle withdrawal and differentiation, which are normally induced by serum deprivation. Among the many mRNAs that are down-regulated by miR-206, the p180 subunit of DNA polymerase α and three other genes are shown to be direct targets. Down-regulation of the polymerase inhibits DNA synthesis, an important component of the differentiation program. The direct targets are decreased by mRNA cleavage that is dependent on predicted microRNA target sites. Unlike small interfering RNA–directed cleavage, however, the 5′ ends of the cleavage fragments are distributed and not confined to the target sites, suggesting involvement of exonucleases in the degradation process. In addition, inhibitors of myogenic transcription factors, Id1-3 and MyoR, are decreased upon miR-206 introduction, suggesting the presence of additional mechanisms by which microRNAs enforce the differentiation program.

scholarly journals In vitro suppression of the MMP-3 gene in normal and cytokine-treated human chondrosarcoma using small interfering RNA

2009 ◽  
Vol 4 (1) ◽  
Author(s):  
Korakot Nganvongpanit ◽  
Patama Chaochird ◽  
Puntita Siengdee ◽  
Peraphan Pothacharoen ◽  
Kasisin Klunklin ◽  
...  
Keyword(s):  
Small Interfering Rna ◽  
Human Chondrosarcoma ◽  
Interfering Rna

scholarly journals Molecular Determinants of Oocyte Competence: Potential Functional Role for Maternal (Oocyte-Derived) Follistatin in Promoting Bovine Early Embryogenesis

Endocrinology ◽  
2009 ◽  
Vol 150 (5) ◽  
pp. 2463-2471 ◽  
Author(s):  
Kyung-Bon Lee ◽  
Anilkumar Bettegowda ◽  
Gabbine Wee ◽  
James J. Ireland ◽  
George W. Smith
Keyword(s):  
Small Interfering Rna ◽  
Functional Role ◽  
Early Embryogenesis ◽  
Type I ◽  
Blastocyst Development ◽  
Oocyte Competence ◽  
Cell Numbers ◽  
Positive Effects ◽  
Interfering Rna

Previous studies established a positive relationship between oocyte competence and follistatin mRNA abundance. Herein, we used the bovine model to test the hypothesis that follistatin plays a functional role in regulation of early embryogenesis. Treatment of early embryos with follistatin during in vitro culture (before embryonic genome activation) resulted in a dose-dependent decrease in time to first cleavage, increased numbers of blastocysts, and increased blastocyst total and trophectoderm cell numbers. To determine the requirement of endogenous follistatin for early embryogenesis, follistatin ablation/replacement studies were performed. Microinjection of follistatin small interfering RNA into zygotes reduced follistatin mRNA and protein and was accompanied by a reduction in number of embryos developing to eight- to 16-cell and blastocyst stages and reduced blastocyst total and trophectoderm cell numbers. Effects of follistatin ablation were rescued by culture of follistatin small interfering RNA-injected embryos in the presence of exogenous follistatin. To investigate whether follistatin regulation of early embryogenesis is potentially mediated via inhibition of endogenous activin activity, the effects of treatment of embryos with exogenous activin, SB-431542 (inhibitor of activin, TGF-β, and nodal type I receptor signaling) and follistatin plus SB-431542 were investigated. Activin treatment mimicked positive effects of follistatin on time to first cleavage and blastocyst development, whereas negative effects of SB-431542 treatment were observed. Stimulatory effects of follistatin on embryogenesis were not blocked by SB-431542 treatment. Results support a functional role for oocyte-derived follistatin in bovine early embryogenesis and suggest that observed effects of follistatin are likely not mediated by classical inhibition of activin activity.

scholarly journals Natural Polysaccharides for siRNA Delivery: Nanocarriers Based on Chitosan, Hyaluronic Acid, and Their Derivatives

Molecules ◽  
2019 ◽  
Vol 24 (14) ◽  
pp. 2570 ◽  
Author(s):  
Inés Serrano-Sevilla ◽  
Álvaro Artiga ◽  
Scott G. Mitchell ◽  
Laura De Matteis ◽  
Jesús M. de la Fuente
Keyword(s):  
Drug Delivery ◽  
Hyaluronic Acid ◽  
Small Interfering Rna ◽  
Drug Delivery Systems ◽  
Sirna Delivery ◽  
Delivery Systems ◽  
Low Toxicity ◽  
Interfering Rna

Natural polysaccharides are frequently used in the design of drug delivery systems due to their biocompatibility, biodegradability, and low toxicity. Moreover, they are diverse in structure, size, and charge, and their chemical functional groups can be easily modified to match the needs of the final application and mode of administration. This review focuses on polysaccharidic nanocarriers based on chitosan and hyaluronic acid for small interfering RNA (siRNA) delivery, which are highly positively and negatively charged, respectively. The key properties, strengths, and drawbacks of each polysaccharide are discussed. In addition, their use as efficient nanodelivery systems for gene silencing applications is put into context using the most recent examples from the literature. The latest advances in this field illustrate effectively how chitosan and hyaluronic acid can be modified or associated with other molecules in order to overcome their limitations to produce optimized siRNA delivery systems with promising in vitro and in vivo results.

scholarly journals Consumption of Fresh Yellow Onion Ameliorates Hyperglycemia and Insulin Resistance in Breast Cancer Patients During Doxorubicin-Based Chemotherapy: A Randomized Controlled Clinical Trial

2016 ◽  
Vol 16 (3) ◽  
pp. 276-289 ◽  
Author(s):  
Farnaz Jafarpour-Sadegh ◽  
Vahid Montazeri ◽  
Ali Adili ◽  
Ali Esfehani ◽  
Mohammad-Reza Rashidi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Insulin Resistance ◽  
Clinical Trial ◽  
Ductal Carcinoma ◽  
Fasting Blood Glucose ◽  
Controlled Clinical Trial ◽  
Random Allocation ◽  
Breast Cancer Patients ◽  
Care Givers

Purpose. Doxorubicin has been found to be associated with insulin resistance in animal models. Onion, a so-called functional food, is noted to affect the insulin signaling pathway of diabetes in vitro. To our knowledge, this is the first study to investigate the effects of consuming fresh yellow onions on insulin-related indices compared with a low–onion-containing diet among breast cancer (BC) patients treated with doxorubicin. Methods. This parallel-design, randomized, triple-blind, controlled clinical trial was conducted on 56 eligible BC patients (aged 30-63 years), diagnosed with invasive ductal carcinoma. Following their second cycle of chemotherapy, subjects were assigned in a stratified-random allocation to receive body mass index–dependent 100 to 160 g/d of onion as high onion group (HO; n = 28) or 30 to 40 g/d small onions in low onion group (LO; n = 28) for 8 weeks intervention. Participants, care givers, and those who assessed laboratory analyses were blinded to the assignments (IRCT Registry No.: IRCT2012103111335N1). Results. The compliance level of participants in the analysis was as high as 87.85%. A total of 23 available cases was analyzed in each group. The daily use of HO resulted in a significant decrease in serum fasting blood glucose and insulin levels in comparison with LO, over the period of study ( P < .001). Posttreatment with HO showed a significant decrease in homeostasis model of assessment-insulin resistance relative to changes in the LO group ( P < .05). A comparison of the changes that occurred throughout pre- and postdose treatments indicated improved quantitative insulin sensitivity check index ( P < .05) and controls on C-peptide in the HO group ( P < .05). Conclusions. The present study demonstrated the effectiveness of onion to ameliorate hyperglycemia and insulin resistance in BC during doxorubicin-based chemotherapy.

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