scholarly journals SUN-LB22 PLK1 as a New Treatment Target for Adrenocortical Carcinoma

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Gabrielle Smith ◽  
Raimunde Liang ◽  
Vasileios Chortis ◽  
Sana Khan ◽  
Juliane Lippert ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Adrenocortical Carcinoma ◽  
Cell Apoptosis ◽  
Cancer Type ◽  
Solid Organ ◽  
Treatment Target ◽  
Significant Difference ◽  
H295r Cells ◽  
Plk1 Expression

Abstract Background: Adrenocortical carcinoma (ACC) is an aggressive malignancy with limited medical treatment options. We previously identified polo-like kinase 1 (PLK1) as one of most overexpressed genes in ACC; thus PLK1 represents a potential treatment target for this cancer type. Some PLK1 inhibitors are under evaluation in clinical trials for other solid organ malignancies, and seem to be more effective in TP53 mutated tumours. The aim of this study was to evaluate PLK1 protein levels in a large series of ACC and assess the in vitroefficacy of PLK1 inhibitors in two different ACC cell lines. Methods: 104 formalin-fixed paraffin-embedded ACC tissue samples with available genetic data were investigated. Nuclear PLK1 protein expression was evaluated by immunohistochemistry and a semi-quantitative H-score was calculated. PLK1 expression levels were correlated to clinical and histological parameters. Efficacy of PLK1-specific inhibitor Volasertib (0-200 nM) was tested in the standard NCI-H295R ACCcell line, which presents PLK-1 overexpression and a large TP53 deletion, and in the newly established MUC1 cell line, which bears a frameshift mutation in TP53. Cell proliferation was analysed using DNA fluorescence and cell apoptosis by Caspase Glo 3/7 assay. Results: Nuclear PLK1 expression was classified as high in 59% of ACC samples, with a significant difference noted between TP53-mutated (n=24) and wild-type (n=80) cases (87.5 vs 51%, p<0.01). PLK1 levels did not correlate with either progression-free or overall survival. H295R cells showed a significant time- and dose-dependent reduction of cell proliferation compared to vehicle control after 72h of Volasertib treatment (p<0.005 per trend, p=0.01 by 200nM by non-parametric two-way ANOVA). A less pronounced and non-significant trend towards inhibited proliferation was observed in MUC1 cells. Cell apoptosis was significantly higher in the H295R cells treated with 175nM and 200nM Volasertib when compared to control (p<0.05), while there was no significant difference in MUC1 cells. Conclusion:In this pilot study, we propose PLK1 inhibitors as promising candidates for treatment of a subset of ACC patients that may be pre-selected according to the tumour molecular pattern. We plan to extend functional experiments to further PLK1 inhibitors, including additional ACC cell lines with a different molecular profile.

scholarly journals Long Non-Coding RNA PVT1/miR-150/ HIG2 Axis Regulates the Proliferation, Invasion and the Balance of Iron Metabolism of Hepatocellular Carcinoma

2018 ◽  
Vol 49 (4) ◽  
pp. 1403-1419 ◽  
Author(s):  
Yunxiuxiu Xu ◽  
Xinxi Luo ◽  
Wenguang He ◽  
Guangcheng Chen ◽  
Yanshan Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Iron Metabolism ◽  
Cell Apoptosis ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Non Coding Rna ◽  
Long Non Coding Rna

Background/Aims: To investigate the biological roles and underlying molecular mechanisms of long non-coding RNA (lncRNA) PVT1 in Hepatocellular carcinoma (HCC). Methods: qRT-PCR was performed to measure the expression of miRNA and mRNA. Western blot was performed to measure the protein expression. CCK-8 assay was performed to determine cell proliferation. Flow cytometry was performed to detect cell apoptosis. Wounding-healing assay and Transwell assay was performed to detect cell migration and invasion. Dual luciferase reporter assay was performed to verify the target relationship. Quantichrom iron assay was performed to check uptake level of cellular iron. Results: PVT1 expression was up-regulated in HCC tissues and cell lines. Function studies revealed that PVT1 knockdown significantly suppressed cell proliferation, migration and invasion, and induced cell apoptosis in vitro. Furthermore, PVT1 could directly bind to microRNA (miR)-150 and down-regulate miR-150 expression. Hypoxia-inducible protein 2 (HIG2) was found to be one target gene of miR-150, and PVT1 knockdown could inhibit the expression of HIG2 through up-regulating miR-150 expression. In addition, the expression of miR-150 was down-regulated, while the expression of HIG2 was up-regulated in HCC tissues and cell lines. Moreover, inhibition of miR-150 could partly reverse the biological effects of PVT1 knockdown on proliferation, motility, apoptosis and iron metabolism in vitro, which might be associated with dysregulation of HIG2. In vivo results showed that PVT1 knockdown suppressed tumorigenesis and iron metabolism disorder by regulating the expression of miR-150 and HIG2. Conclusion: Taken together, the present study demonstrates that PVT1/miR-150/HIG2 axis may lead to a better understanding of HCC pathogenesis and provide potential therapeutic targets for HCC.

scholarly journals LINC01121 Inhibits Cell Apoptosis While Facilitating Proliferation, Migration, and Invasion Though Negative Regulation of the Camp/PKA Signaling Pathway via GLP1R

2018 ◽  
Vol 47 (3) ◽  
pp. 1007-1024 ◽  
Author(s):  
Yi-Gang Qian ◽  
Zhou Ye ◽  
Hai-Yong Chen ◽  
Zhen Lv ◽  
Ai-Bin Zhang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Microarray Data ◽  
Cell Apoptosis ◽  
Migration And Invasion ◽  
Protein Levels ◽  
Pancreatic Cancer Cells ◽  
Significant Difference

Background/Aims: Pancreatic cancer is an aggressive malignancy as a result of highly metastatic potential. The current study was carried out to alter the expression of LINC01121 in pancreatic cancer, with the aim of elucidating its effects on the biological processes of cell proliferation, migration, invasion, and apoptosis. We hypothesized that both the GLP1R gene and cAMP/PKA signaling pathway participate in the aforementioned process. Methods: Microarray data (GSE14245, GSE27890 and GSE16515) and annotating probe files linked to pancreatic cancer were downloaded through the GEO database. The Multi Experiment Matrix (MEM) site was used to predict the target gene of lncRNA. Both pancreatic cancer tissues (n = 56) and paracancerous tissues (n = 45) were collected from patients diagnosed with pancreatic cancer. Immunohistochemistry was applied to identify the positive expression rate of GLP1R protein. Isolated pancreatic cancer cells and PANC-1 cells were independently classified into the blank, negative control (NC), LINC01121 vector, siRNA-LINC01121, siRNA-GLP1R and siRNA-LINC01121 + siRNA-GLP1R groups. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis were applied to detect the expressions of LINC01121, GLP1R, cAMP, PKA, CREB, Bcl-2, Bad and PCNA. Cell proliferation, migration, invasion, cycle progression, and apoptosis were examined by MTT assay, scratch test, Transwell assay and flow cytometry analyses of Annexin V-FITC/PI staining. Results: Observations were made indicating that LINC01121 was highly expressed, while low expressions of GLP1R in pancreatic cancer were detected based on microarray data, which was largely in consistent with the data collected of LINC01121 and GLP1R within the tissues. The target prediction program and luciferase activity analysis was testament to the notion suggesting that GLP1R was indeed a target of LINC01121. In contrast to the blank and NC groups, the LINC01121 vector group exhibited increased expressions of LINC01121; decreased mRNA and protein levels of GLP1R, Bad, cAMP, and PKA; increased protein levels of CREB, Bcl-2, PCNA, p-PKA and p-CREB; increased cell proliferation, migration and invasion; and decreased cell apoptosis. There was no significant difference detected among the blank, NC, and siRNA-LINC01121 + siRNA-GLP1R groups, except that decreased LINC01121 expression was determined in the siRNA-LINC01121 + siRNA-GLP1R group. Parallel data were observed in the pancreatic cancer cells and PANC-1 cells. Conclusion: The current study presents evidence indicating that LINC01121 might inhibit apoptosis while acting to promote proliferation, migration, and invasion of pancreatic cancer cells, supplementing the stance held that LINC01121 functions as a tumor promoter by means of its involvement in the process of translational repression of the GLP1R and inhibition of the cAMP/PKA signaling pathway.

scholarly journals A Novel Gene RNF138 Expressed in Human Gliomas and Its Function in the Glioma Cell Line U251

2012 ◽  
Vol 35 (3) ◽  
pp. 167-178 ◽  
Author(s):  
You-xin Zhou ◽  
San-song Chen ◽  
Ting-feng Wu ◽  
Da-dong Ding ◽  
Xiong-hui Chen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Line ◽  
Brain Tissue ◽  
Cell Lines ◽  
Cell Apoptosis ◽  
Glioma Cell ◽  
Glioma Cell Line ◽  
Glioma Tissue ◽  
Glioma Cell Lines

Background: The gliomas represent the most common primary malignant brain tumors; however, little is known about the molecular pathogenesis of these tumors. Recent research reveals that the oncogenesis and development of gliomas have a close relation to the overexpression of several oncogenes and the inactivation of tumor suppressor genes. Whether the RING finger protein, RNF138, a newly discovered protein, plays a role in glioma oncogenesis is unknown. The present study investigates the expression levels of RNF138 mRNA in glioma samples and noncancerous brain samples and its function in the human glioma cell line U251.Methods: RT-PCR was used to ascertain the expression of RNF138 mRNA in the glioma cell lines U251, SHG44, U87, A172, and U373. The RNF138 mRNA expression levels of 35 pathological confirmed glioma samples (Grade I – 4 cases, Grade II – 13 cases, Grade III – 11 cases, and Grade IV – 7 cases) and five noncancerous brain tissue samples were analyzed by real-time quantitative PCR. By RNA interference (RNAi) with the lentivirus vector system, the expression of RNF138 was inhibited in the human astrocytomas-glioblastoma multiforme cell line U251. The effects of RNF138-knockdown on cell proliferation were assessed by Cellomics, and cell cycle and cell apoptosis were assessed by FACS.Results: The RNF138 mRNA is expressed in the five glioma cell lines, and its expression level is significantly higher in glioma tissue than in noncancerous brain tissue. By down-regulation of RNF138 expression, U251 cell proliferation was inhibited and cell apoptosis increased. At the same time, S stage cells lessened and G2 stage cells increased.Conclusion: The RNF138 gene is highly expressed in glioma tissue and glioma cell lines. It plays an important role in glioma cell proliferation, apoptosis, and cell cycle.

scholarly journals Effects of LncRNA-HOST2 on cell proliferation, migration, invasion and apoptosis of human hepatocellular carcinoma cell line SMMC-7721

2017 ◽  
Vol 37 (2) ◽  
Author(s):  
Run-Tian Liu ◽  
Jing-Lin Cao ◽  
Chang-Qing Yan ◽  
Yang Wang ◽  
Cong-Jing An ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Cell Line ◽  
Cell Lines ◽  
Cell Apoptosis ◽  
Human Hepatocellular Carcinoma ◽  
Migration And Invasion ◽  
Normal Tissues ◽  
Experimental Group

The present study explored the effect of long non-coding RNA-human ovarian cancer-specific transcript 2 (LncRNA-HOST2) on cell proliferation, migration, invasion and apoptosis of human hepatocellular carcinoma (HCC) cell line SMMC-7721. HCC tissues and adjacent normal tissues from 162 HCC patients were collected. The HCC cell lines were assigned into the control group (regular culture), negative control (NC) group (transfected with siRNA) and experimental group (transfected with Lnc-HOST2 siRNA). Quantitative real-time PCR (qRT-PCR) was used to detect the expression of LncRNA-HOST2. Cell proliferation was detected by CCK-8 and colony-forming assays, cell apoptosis by flow cytometry and cell migration by Scratch test. Transwell assay was used to evaluate cell migration and invasion abilities. LncRNA-HOST2 expression in the HCC tissues increased 2–10 times than that in the adjacent normal tissues. Compared with the HL-7702 cell line, LncRNA-HOST2 expression in HepG2, SMMC-7721 and Huh7 cell lines was all up-regulated, but the SMMC-7721 cell had the highest Lnc-HOST2 expression. The LncRNA-HOST2 expression in the experimental group was down-regulated as compared with the control and NC groups. In comparison with the control and NC groups, cloned cells reduced, cell apoptosis increased, clone-forming ability weakened and inhibitory rate of colony formation increased in the experimental group. The cells migrating and penetrating into the transwell chamber were fewer in the experimental group than those in the control and NC groups. The experimental group exhibited slow wound healing and decreased cell migration area after 48 h. These findings indicate that LncRNA-HOST2 can promote cell proliferation, migration and invasion and inhibit cell apoptosis in human HCC cell line SMMC-7721.

scholarly journals Silencing of miR-17-5p suppresses cell proliferation and promotes cell apoptosis by directly targeting PIK3R1 in laryngeal squamous cell carcinoma

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jian-Xing Wang ◽  
Xin-Ju Jia ◽  
Yan Liu ◽  
Jin-Hui Dong ◽  
Xiu-Min Ren ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Tumor Progression ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Squamous Cell ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Laryngeal Squamous Cell Carcinoma

Abstract Background Increasing evidence has suggested that microRNAs (miRNAs) act as key post-transcriptional regulators in tumor progression. Previous studies have confirmed that miR-17-5p functions as an oncogene in multiple cancers and contributes to tumor progression. However, the role and biological functions of miR-17-5p in the development of laryngeal squamous cell carcinoma (LSCC) still remain unknown. Methods qRT-PCR was used to detect miRNA and mRNA expression levels in LSCC tissues and cell lines. CCK-8 assay was used to measure cell viability and flow cytometry was performed to evaluate cell apoptosis. Western blot analysis was used to detect the protein levels of BAX, BCL-2, cleaved Caspase-3, PIK3R1 and AKT. Luciferase reporter assay was used to detect the effect of miR-17-5p on PIK3R1 expression. Xenograft animal model was used to test the effect of miR-17-5p on LSCC cell in vivo. Results In the present study, we found that miR-17-5p expression level was upregulated in LSCC tissues and cell lines. Depletion of miR-17-5p in LSCC cells significantly reduced cell proliferation and promoted cell apoptosis in vitro and in vivo. Mechanically, knockdown of miR-17-5p in LSCC cells inhibited BCL-2 expression while enhanced BAX and cleaved Caspase-3 protein expression. Moreover, depletion of miR-17-5p in LSCC cells suppressed AKT phosphorylation but did not influence PTEN expression. Importantly, miR-17-5p positively regulated PIK3R1 expression by directly binding to its 3′-untranslated region (UTR). Additionally, PIK3R1, which expression was downregulated in LSCC tissues and cell lines, was involved in LSCC cell survival by modulating the activation of AKT signal pathway. Dysregulation of miR-17-5p/PIK3R1 axis was participated in LSCC cell proliferation and apoptosis by inhibiting the activation of the PI3K/AKT signaling pathway. Conclusions In conclusion, our study indicates that the miR-17-5p/PIK3R1 axis plays an essential role in the development of LSCC and provides a potential therapeutic target for LSCC treatment.

scholarly journals Downregulated Long Noncoding RNA PART1 Inhibits Proliferation and Promotes Apoptosis in Bladder Cancer

2019 ◽  
Vol 18 ◽  
pp. 153303381984663 ◽  
Author(s):  
Xin Hu ◽  
Hefei Feng ◽  
Huaxing Huang ◽  
Wei Gu ◽  
Qiuyu Fang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Bladder Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Ribonucleic Acid ◽  
Cell Apoptosis ◽  
Bladder Cancer Cell ◽  
Proliferation And Apoptosis ◽  
Proliferation And Invasion

Objective: In this study, we aimed to clarify the effects of long noncoding ribonucleic acid prostrate androgen-regulated transcript-1 on bladder cancer cell proliferation and apoptosis. Methods: Microarrays were implemented to investigate the long noncoding ribonucleic acid expression profiles in bladder cancer tissue (N = 9) and in noncancer bladder tissue (N = 5). Relative prostrate androgen-regulated transcript-1 expression levels in tissue samples or cell lines were detected by real-time quantitative reverse transcription-polymerase chain reaction. Prostrate androgen-regulated transcript-1 expression was enhanced by the transfection of pcDNA3.1-prostrate androgen-regulated transcript-1 and downregulated by the infection with pcMV-sh prostrate androgen-regulated transcript-1. Additionally, cell proliferation and apoptosis were measured by the cell counting kit-8 assay and flow cytometry, respectively. Cell invasion was determined by a Transwell assay. Results: Prostrate androgen-regulated transcript-1 expression was upregulated in bladder cancer tissues compared to adjacent nontumor tissues. Furthermore, prostrate androgen-regulated transcript-1 levels were successfully upregulated by pcDNA3.1-prostrate androgen-regulated transcript-1 and depleted by pCMV-sh prostrate androgen-regulated transcript-1 in bladder cancer cell lines (5637, T24). Enhanced prostrate androgen-regulated transcript-1 expression promoted cell proliferation and invasion and inhibited cell apoptosis. However, knockdown of prostrate androgen-regulated transcript-1 expression inhibited cell proliferation and invasion and induced cell apoptosis. Conclusion: In summary, these data suggest that the knockdown of prostrate androgen-regulated transcript-1 represents a tumor suppressor player in bladder cancer and contributes to the inhibition of tumor proliferation, the promotion of cell apoptosis, and the suppression of cell invasion. Prostrate androgen-regulated transcript-1 may function as a new prognostic biomarker and as a feasible therapeutic target for patients with bladder cancer.

scholarly journals miR-1258 Regulates Cell Proliferation and Cell Cycle to Inhibit the Progression of Breast Cancer by Targeting E2F1

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Xianbao Zhao
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Cell Apoptosis ◽  
Luciferase Assay ◽  
G1 Phase ◽  
Breast Epithelial Cell ◽  
Epithelial Cell Lines ◽  
Growth Activity

Objective. This study is designed to clarify that miR-1258 targets E2F1 to regulate the proliferation and cell cycle of breast cancer (BC) cells and consequently suppress the progression of BC. Methods. Bioinformatics analysis was used to analyze the differentially expressed genes in BC. The expression of miR-1258 and E2F1 mRNA in BC cell lines and immortalized breast epithelial cell lines were detected by qRT-PCR. The proliferation and growth activity of BC cells were detected by MTT and colony formation assays. The apoptosis and cell cycle of BC cells were detected by flow cytometry and the targeting relationship between miR-1258 and E2F1 was identified by dual-luciferase assay. Results. The expression of miR-1258 was decreased while that of E2F1 was increased in BC cells. Overexpression of miR-1258 and silencing E2F1 could inhibit the cell proliferation and growth, block cells in the G0/G1 phase, and promote cell apoptosis. Besides, miR-1258 inhibited cell proliferation and growth, block cells in the G0/G1 phase, and promote cell apoptosis by downregulating E2F1. Conclusion. miR-1258 regulates the proliferation and cell cycle to inhibit the progression of BC by targeting and downregulating E2F1.

MiR-129-5p promotes radio-sensitivity of NSCLC cells by targeting SOX4 and RUNX1

2021 ◽  
Vol 21 ◽  
Author(s):  
Tongqing Xue ◽  
Gang Yin ◽  
Weixuan Yang ◽  
Xiaoyu Chen ◽  
Cheng liu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Transcription Factor ◽  
Cell Lines ◽  
Cell Apoptosis ◽  
Colony Formation ◽  
Nsclc Cell ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Radio Sensitivity

Background: Dysregulation of microRNAs (miRNAs) figures prominently in radio-sensitivity of non-small cell lung cancer (NSCLC). MiR-129-5p can block the development of a variety of tumors. However, whether miR-129-5p modulates radio-sensitivity of NSCLC cells remains unknown. Objective: This study was aimed to explore the role and the underlying mechanism of miR-129-5p in the radiosensitivity of NSCLC. Methods: Radio-resistant NSCLC cell lines (A549-R and H1299-R) were constructed using A549 and H1299 cells. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to quantify miR-129-5p, SRY-box transcription factor 4 (SOX4) mRNA, and RUNX family transcription factor 1 (RUNX1) mRNA expression levels. Cell apoptosis and cell cycle were detected by flow cytometry. Cell counting kit-8 (CCK-8) assay and colony formation experiments were used to measure cell proliferation. γ-H2AX was examined by Western blot to confirm DNA injury. Dual-luciferase reporter experiments were applied to analyze the interactions among miR-129-5p, RUNX1, and SOX4. Results: In A549-R and H1299-R cells, compared with the wild type cell lines, miR-129-5p expression was remarkably reduced while SOX4 and RUNX1 expressions were increased. The transfection of miR-129-5p into NSCLC cell lines, markedly induced cell apoptosis, DNA injury, and cell cycle arrest, and inhibited cell proliferation and colony formation. RUNX1 and SOX4 were validated as target genes of miR-129-5p, and the restoration of RUNX1 or SOX4 could counteract the influence of miR-129-5p on A549-R cells. Conclusion: MiR-129-5p sensitizes A549-R and H1299-R cells to radiation by targeting RUNX1 and SOX4.

HHT-Induced Cell Apoptosis Is Associated with Reduction of Survivin mRNA Expression.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4364-4364
Author(s):  
Zhen Cai ◽  
Hanying Bao
Keyword(s):  
Cell Death ◽  
Mrna Expression ◽  
Cell Lines ◽  
Cell Apoptosis ◽  
Molecular Mechanisms ◽  
Apoptotic Cell ◽  
Survivin Expression ◽  
Theoretical Ground ◽  
Survivin Mrna ◽  
Significant Difference

Abstract The inhibitor of apoptosis (IAP) gene family, which was discovered less than a decade ago, encodes a group of structurally related proteins that, in addition to their ability to suppress apoptotic cell death, are involved in an increasing number of seemingly unrelated cellular functions. The IAP families have evolved as highly conserved regulators of cell death. Homoharringtonine(HHT) is a plant alkaloid with antileukemia activity which is currently tested for treatment of acute and chronic leukemia. Our previous study suggested that HHT could induced apoptosis of MUTZ-1 in vitro, but little is know about the possible molecular mechanisms of HHT induced cell apoptosis. The study on the mechanisms of HHT in regulation of apoptosis will give us insight into further understanding of the role HHT. The data generated from this study will also provide theoretical ground for making use of HHT in clinical treatment. In this study, five cell lines including MUTZ-1, K562, Jurkat, RMPI and HL60 were used in the experiments to detect the effects of HHT on the induction of apoptosis and to study the possible mechanisms of HHT in regulation of apoptosis of the cells. Cell apoptosis were observed by flow cytometry (FCM). Cell apoptotic morphology was observed by transmission electron microscope. Semi-quantitative RT-PCR was used to evaluate the mRNA expression of survivin, XIAP, Bcl-2 and Bax in these cells. Our results demonstrated that HHT was capable of inducing apoptosis in all the five cell lines, with an increasing apoptotic rate in the order of K562, MUTZ-1/RMPI, and Jurkat/HL60, at a HHT concentration of 0.1 μg/ml for 12 hours (p<0.05). Survivin mRNA was not detected without HHT treatment but was detected in all the five cell lines after induction with HHT. Interestingly, the level of survivin mRNA expression was detected in the same but reversed order as with apoptotic rate: cell lines showed lowest apoptotic rate had highest survivin mRNA level, indicating a negative correlation between the two (p=0.003). The expression of Bcl-2 and Bax mRNA showed no significant correlation to HHT-induced apoptotic rate. There was no significant difference in XIAP expression in the 5 cell lines. We conclude that HHT might act via reduction of survivin expression and the level of survivin mRNA may serve as a predictor for chemotherapy sensitivity to HHT.

scholarly journals microRNA-802 inhibits epithelial-mesenchymal transition through targeting flotillin-2 in human prostate cancer

2017 ◽  
Vol 37 (2) ◽  
Author(s):  
Dawei Wang ◽  
Guoliang Lu ◽  
Yuan Shao ◽  
Da Xu
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Cell Apoptosis ◽  
Epithelial Mesenchymal Transition ◽  
Xenograft Model ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Mesenchymal Transition

miRNAs are a class of non-coding RNAs that exert critical roles in various biological processes. The aim of the present study was to identify the functional roles of miR-802 in regulating epithelial–mesenchymal transition (EMT) in prostate cancer (PCa). miR-802 expression was detected in 73 pairs of PCa samples and PCa cell lines (PC3 and DU145 cells) by qRT-PCR. Cell proliferation was detected using MTT assay, and cell apoptosis was evaluated using flow cytometry. Transwell assay was conducted to investigate cell migration and invasion. Expression analysis of a set of EMT markers was performed to explore whether miR-802 is involved in EMT program. Xenograft model was established to investigate the function of miR-802 in carcinogenesis in vivo. The direct regulation of Flotillin-2 (Flot2) by miR-802 was identified using luciferase reporter assay. miR-802 was remarkably down-regulated in PCa tissues and cell lines. Gain-of-function trails showed that miR-802 serves as an ‘oncosuppressor’ in PCa through inhibiting cell proliferation and promoting cell apoptosis in vitro. Overexpression of miR-802 significantly suppressed in vivo PCa tumor growth. Luciferase reporter analysis identified Flot2 as a direct target of miR-802 in PCa cells. Overexpressed miR-802 significantly suppressed EMT, migration and invasion in PCa cells by regulating Flot2. We identified miR-802 as a novel tumor suppressor in PCa progression and elucidated a novel mechanism of the miR-802/Flot2 axis in the regulation of EMT, which may be a potential therapeutic target.

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