Study on the correlation between the expression of basic transcription factor 3 (BTF3) and the efficacy and prognosis of patients with malignant melanoma (MM).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21554-e21554
Author(s):  
Ning Ning Niu ◽  
Yong Qi Li ◽  
Liang Guo ◽  
Qiong Yang Liu ◽  
Yi Qun Zhang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
Nude Mice ◽  
Tumor Formation ◽  
Small Sample ◽  
Unknown Primary ◽  
Retrospective Clinical Study ◽  
Resected Stage ◽  
Sirna Group ◽  
Low Expression

e21554 Background: BTF3 is an RNA polymerase II transcription factor, studies have confirmed that BTF3 is abnormally expressed in several types of tumors and closely related to the proliferation and prognosis of gastrointestinal tumors. However, the function of BTF3 in MM remains unknown. The present study aim to detect the expression and proliferation of BTF3，to explore the correlation between the BTF3 expression and the efficacy and prognosis of MM patients. Methods: We explored the effect of BTF3 through silencing BTF3 expression by siRNA transfection with lentivirus in human melanoma cell lines. The cell proliferation, cell cycle and apoptosis were determined by methyl-thaizolyl-tetrazolium assay, flow cytometry and western blot, respectively. Then we investigated the effect of BTF3 in nude mice by tumor formation experiment. The expression of BTF3 was determined by immunohistochemistry (IHC) from 32 patients with different subtypes of MM during October 2014 to October 2020. Among them, 28 cases could be resected (stage I-III), 4 cases could not be resected (stage III-IV). Cutaneous MM 7 cases, Acral MM 14 cases, mucosal MM 9 cases, unknown primary MM 2 cases. The correlation of BTF3 expression and RFS (recurrence-free survival) /OS (overall survival) in 28 patients with resected MM was explored by Student’s t test. Results: The increased viability of negative control virus infection group was 4.706 times than that of BTF3-siRNA group. Compared with the former, BTF3-siRNA group had more cells in G1 and S phase (P< 0.05) and more apoptotic cells (P< 0.05). BTF3-siRNA reduced tumor formation in the nude mice (P<0.01). The relative IHC scores of BTF3 was 5.50±3.19 in tumor tissues (the higher the score, the higher the expression of BTF3), 6.52±4.13 in adjacent noncancerous tissues. The expression of BTF3 in different subtypes of MM tissues are shown in the table. In the median follow-up time of 27 months (6-68 months), 13 cases survived without recurrence or metastasis, 10 cases survived with recurrence or metastasis, 8 cases died. In 28 resectable MM patients, the median RFS/OS of high BTF3 expression (IHC score>5) and low expression (IHC score:0-4) were 18.57 / 24.62 months and 20.42 / 22.78 months. The corresponding RFS/OS P values of patients with high and low expression were 0.323 and 0.607. Conclusions: The study suggests that BTF3 play a role in the proliferation, cell cycle regulation, apoptosis and tumorigenicity of MM. Preliminary small-sample retrospective clinical study did not suggest that BTF3 was related to the efficacy and prognosis of patients, which needs to be further verified by large-sample prospective studies.[Table: see text]

Genes that can bypass the CLN requirement for Saccharomyces cerevisiae cell cycle START

1994 ◽  
Vol 14 (3) ◽  
pp. 2041-2047
Author(s):  
C B Epstein ◽  
F R Cross
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Transcription Factor ◽  
Copy Number ◽  
Single Gene ◽  
Low Copy Number ◽  
Synthetically Lethal ◽  
Low Expression

Cell cycle START in Saccharomyces cerevisiae requires at least one of the three CLN genes (CLN1, CLN2, or CLN3). A total of 12 mutations bypassing this requirement were found to be dominant mutations in a single gene that we named BYC1 (for bypass of CLN requirement). We also isolated a plasmid that had cln bypass activity at a low copy number; the gene responsible was distinct from BYC1 and was identical to the recently described BCK2 gene. Strains carrying bck2::ARG4 disruption alleles were fully viable, but bck2::ARG4 completely suppressed the cln bypass activity of BYC1. swi4 and swi6 deletion alleles also efficiently suppressed BYC1 cln bypass activity; Swi4 and Swi6 are components of a transcription factor previously implicated in control of CLN1 and CLN2 expression. bck2::ARG4 was synthetically lethal with cln3 deletion, suggesting that CLN1 and CLN2 cannot function in the simultaneous absence of BCK2 and CLN3; this observation correlates with low expression of CLN1 and CLN2 in bck2 strains deprived of CLN3 function. Thus, factors implicated in CLN1 and CLN2 expression and/or function are also required for BYC1 function in the absence of all three CLN genes; this may suggest the involvement of other targets of Swi4, Swi6, and Bck2 in START.

scholarly journals Dual Roles for NFAT Transcription Factor Genes as Oncogenes and Tumor Suppressors

2008 ◽  
Vol 28 (23) ◽  
pp. 7168-7181 ◽  
Author(s):  
Bruno K. Robbs ◽  
Andre L. S. Cruz ◽  
Miriam B. F. Werneck ◽  
Giuliana P. Mognol ◽  
João P. B. Viola
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Cell Transformation ◽  
Tumor Formation ◽  
3T3 Cells ◽  
Activated T Cells ◽  
Nih 3T3 ◽  
Nih 3T3 Cells

ABSTRACT Nuclear factor of activated T cells (NFAT) was first described as an activation and differentiation transcription factor in lymphocytes. Several in vitro studies suggest that NFAT family members are redundant proteins. However, analysis of mice deficient for NFAT proteins suggested different roles for the NFAT family of transcription factors in the regulation of cell proliferation and apoptosis. NFAT may also regulate several cell cycle and survival factors influencing tumor growth and survival. Here, we demonstrate that two constitutively active forms of NFAT proteins (CA-NFAT1 and CA-NFAT2 short isoform) induce distinct phenotypes in NIH 3T3 cells. Whereas CA-NFAT1 expression induces cell cycle arrest and apoptosis in NIH 3T3 fibroblasts, CA-NFAT2 short isoform leads to increased proliferation capacity and induction of cell transformation. Furthermore, NFAT1-deficient mice showed an increased propensity for chemical carcinogen-induced tumor formation, and CA-NFAT1 expression subverted the transformation of NIH 3T3 cells induced by the H-rasV12 oncogene. The differential roles for NFAT1 are at least partially due to the protein C-terminal domain. These results suggest that the NFAT1 gene acts as a tumor suppressor gene and the NFAT2 short isoform acts gene as an oncogene, supporting different roles for the two transcription factors in tumor development.

scholarly journals High PHD Finger Protein 19 (PHF19) expression predicts poor prognosis in colorectal cancer: a retrospective study

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11551
Author(s):  
Pengfei Li ◽  
Jie Sun ◽  
Yuanyuan Ruan ◽  
Lujun Song
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Western Blot ◽  
Nude Mice ◽  
Tumor Formation ◽  
Tumor Proliferation ◽  
Invasion And Metastasis ◽  
Mesenchymal Transition ◽  
Proliferative Ability

Background Colorectal cancer (CRC) is the third most common cancer all around the world, and it seriously threats human health. PHF19 has been proved to be closely related to the prognosis of patients in a variety of malignant tumors, but the effect of PHF19 on the prognosis evaluation of CRC patients has not been confirmed. Methods In our study, we used GEO, TCGA database and IHC to verify the PHF19 expression in CRC samples. Survival analysis of PHF19 based on TCGA, GEO series, and our own CRC sample were performed. Cox regression was performed to reveal the relationship between PHF19 and prognosis. Co-expression was performed to find genes related to PHF19 expression. GO/KEGG enrichment analysis and GSEA analysis were used to confirm the most relevant signal pathway to PHF19. Next, cell experiments were performed to verify the effect of PHF19 on the proliferation, invasion and metastasis of CRC. Then, Western blot was used to verify the protein expression of the above two phenotypes. Finally, tumor formation experiments in nude mice were used to verify the role of PHF19 of tumor proliferation in vivo. Results We found that PHF19 was significantly over-expressed in tumors compared with normal tissues. Kaplan–Meier (K–M) analysis indicated that high PHF19 in CRC associated with poor overall survival (OS) in CRC patients. Clinical correlation analysis showed that high expression of PHF19 was closely related to t umor progression in CRC patients, especially infiltration and metastasis. Bioinformatics revealed that PHF19 might affect tumor malignant phenotype by regulating the cell cycle in CRC. CCK-8 and clonal formation experiment showed that the proliferative ability of tumor cells was promoted. Flow cytometry showed that the cell cycle accelerated the transition from G1 to S phase. Western blot found that Cyclin D1, CDK4, and CDK6 expression were up-regulated. Transwell and wound-healing experiment found that invasive and migratory abilities was promoted after the over-expression of PHF19. Western blot showed that the expression of key proteins of Epithelial-Mesenchymal Transition (EMT) changed. Tumor formation experiments in nude mice showed that overexpression of PHF19 could promote tumor proliferation in vivo. Conclusion Our research proved that PHF19 could be an independent prognostic factor for CRC, PHF19 promoted the proliferative ability and the invasion and metastasis of CRC by up-regulating the expression of key molecules related to cell cycle and EMT pathway in vitro, promoting tumor proliferation in vivo.

scholarly journals Hsa-miR-557 Inhibits Osteosarcoma Growth Through Targeting KRAS

2022 ◽  
Vol 12 ◽  
Author(s):  
Zhi Qiao ◽  
Jinfeng Li ◽  
Hongwei Kou ◽  
Xiangrong Chen ◽  
Deming Bao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Nude Mice ◽  
Target Genes ◽  
Tumor Formation ◽  
Cell Cycle Analysis ◽  
Luciferase Reporter ◽  
Expression Of Genes ◽  
Therapeutic Molecules

Objective: Osteosarcoma is the most common malignancy in the skeletal system; studies showed an important role of miRNAs in tumorigenesis, indicating miRNAs as possible therapeutic molecules. This study found abnormal hsa-miR-557 expression levels in osteosarcoma and tried to explore the potential function and the mechanism.Methods: Differential expression genes of osteosarcoma were analyzed using GSE28423 from the GEO database. Survival analysis of miRNAs was conducted with data obtained from the TARGET-OS database. STRING and miRDIP were used to predict target genes of hsa-miR-557; KRAS was then verified using dual-luciferase reporter assay. Expression of genes was detected by qPCR, and levels of proteins were detected by Western blot. The proliferation ability of cells was detected by CCK-8 and cell cycle analysis. Tumor formation assay in nude mice was used to detect the influence of osteosarcoma by hsa-miR-557 in vivo.Results: Analysis from the GEO and TARGET databases found 12 miRNAs that are significantly related to the osteosarcoma prognosis, 7 downregulated (hsa-miR-140-3p, hsa-miR-564, hsa-miR-765, hsa-miR-1224-5p, hsa-miR-95, hsa-miR-940, and hsa-miR-557) and 5 upregulated (hsa-miR-362-3p, hsa-miR-149, hsa-miR-96, hsa-miR-744, and hsa-miR-769-5p). CCK-8 analysis and cell cycle analysis found that hsa-miR-557 could significantly inhibit the proliferation of osteosarcoma cells. The tumor formation assay in nude mice showed that tumor sizes and weights were inhibited by hsa-miR-557 transfection. Further studies also proved that hsa-miR-557 could target the 3′UTR of KRAS and modulate phosphorylation of downstream proteins.Conclusion: This study showed that hsa-miR-557 could inhibit osteosarcoma growth both in vivo and in vitro, by modulating KRAS expression.

scholarly journals Genes that can bypass the CLN requirement for Saccharomyces cerevisiae cell cycle START.

1994 ◽  
Vol 14 (3) ◽  
pp. 2041-2047 ◽  
Author(s):  
C B Epstein ◽  
F R Cross
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Transcription Factor ◽  
Copy Number ◽  
Single Gene ◽  
Low Copy Number ◽  
Synthetically Lethal ◽  
Low Expression

Cell cycle START in Saccharomyces cerevisiae requires at least one of the three CLN genes (CLN1, CLN2, or CLN3). A total of 12 mutations bypassing this requirement were found to be dominant mutations in a single gene that we named BYC1 (for bypass of CLN requirement). We also isolated a plasmid that had cln bypass activity at a low copy number; the gene responsible was distinct from BYC1 and was identical to the recently described BCK2 gene. Strains carrying bck2::ARG4 disruption alleles were fully viable, but bck2::ARG4 completely suppressed the cln bypass activity of BYC1. swi4 and swi6 deletion alleles also efficiently suppressed BYC1 cln bypass activity; Swi4 and Swi6 are components of a transcription factor previously implicated in control of CLN1 and CLN2 expression. bck2::ARG4 was synthetically lethal with cln3 deletion, suggesting that CLN1 and CLN2 cannot function in the simultaneous absence of BCK2 and CLN3; this observation correlates with low expression of CLN1 and CLN2 in bck2 strains deprived of CLN3 function. Thus, factors implicated in CLN1 and CLN2 expression and/or function are also required for BYC1 function in the absence of all three CLN genes; this may suggest the involvement of other targets of Swi4, Swi6, and Bck2 in START.

scholarly journals CircFAM114A2 Inhibits Bladder Cancer Proliferation and Promotes Cisplatin Sensitivity via the miR-222-3p/P27 and miR-146a-5p/P21 Cascades

2020 ◽  
Author(s):  
Jiancheng Lv ◽  
Zijian Zhou ◽  
Jingzi Wang ◽  
Xiao Yang ◽  
Hao Yu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Bladder Cancer ◽  
Cancer Progression ◽  
Nude Mice ◽  
Target Genes ◽  
Histological Grade ◽  
Tumor Formation ◽  
Luciferase Reporter ◽  
Circular Rnas

Abstract Background: Circular RNAs (circRNAs) are noncoding RNAs that have the structure of a covalently closed loop. Increasing data has proved that circRNA can influence the development and progression of tumors. CircFAM114A2 is generated from several exons of FAM114A2. However, the function and mechanisms of circFAM114A2 in bladder cancer (BCa) remain unclear. This research aimed to reveal that circFAM114A2 inhibits bladder cancer progression and improves sensitivity of cisplatin chemotherapy by inducing G1/S cell cycle arrest via novel miR-222-3p/P27 and miR-146a-5p/P21 cascades.Methods: Here, to elucidate the potential roles of circFAM114A2 in BCa, we conducted RNA-sequencing on 5 pairs of BCa samples and screened for circRNAs. CircRNAs, microRNAs (miRNAs) and mRNAs, as well as levels of P27 and P21, in human cells and tissues were detected by qRT-PCR and western blot, respectively. CircRNA-miRNA interactions and miRNA-downstream mRNAs interactions were investigated by RNA pull-down assay and fluorescence in situ hybridization (FISH) or luciferase reporter assays, respectively. Then, the function of circFAM114A2 in BCa was explored using cell proliferation, cell cycle and tumorigenesis assays in nude mice. Finally, the function of circFAM114A2 in cisplatin chemo-sensitivity in BCa was detected by IC50 and tumor formation of xenograft in cisplatin-treated nude mice. Results: We discovered that circFAM114A2 levels were decreased in BCa cell lines and tissues. According to follow-up data, BCa patients with higher circFAM114A2 expression had better survival. Importantly, the levels of circFAM114A2 were associated with the histological grade of BCa. Overexpression of circFAM114A2 inhibited cell proliferation and increased sensitivity to cisplatin chemotherapy. Mechanistically, circFAM114A2 directly sponged miR-222-3p/miR-146a-5p and subsequently influenced the expression of the downstream target genes P27/P21, which, in turn, inhibited progression of BCa.Conclusions: CircFAM114A2 acted as a tumor suppressor through a novel circFAM114A2/miR-222-3p/P27 and circFAM114A2/miR-146a-5p/P21 pathway. CircFAM1142 has therefore great potential as a prognostic biomarker and therapeutic target for BCa.

Sign in / Sign up

Export Citation Format

Share Document