scholarly journals Effect of miR‑215 on the Expression of Tumor Suppressor Gene Rb1 in Retinoblastoma Cell Lines

2020 ◽  
Author(s):  
Liqin SHAO ◽  
Zhangxing SHENG ◽  
Yuefeng ZHU ◽  
Jianchao LI ◽  
Rufa MENG
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Cell Lines ◽  
Suppressor Gene ◽  
Clinicopathological Features ◽  
Retinoblastoma Cell ◽  
Reverse Transcription Quantitative Pcr ◽  
Y79 Cells ◽  
Degree Of Differentiation ◽  
Cancer Tissues

Background: Effect of miR-215 on the expression of tumor suppressor gene retinoblastoma (Rb)1 in Rb cell lines was investigated. Methods: A total of 128 patients were selected. The expression of miR‑215 in cancer and adjacent healthy tissues of the 128 patients was detected by reverse transcription-quantitative PCR (RT-qPCR). HXO‑Rb44 and Y79 cell lines were transfected with miR‑215 analogs or miR‑215 inhibitors, and the expression of Rb1 protein in the cell lines was detected by western blotting. Results: The expression of miR-215 in the adjacent healthy tissues of patients was significantly lower than that in cancer tissues (P<0.001). The expression of miR-215 in Y79 and HXO-Rb44 cells was significantly higher than that in APRE-19 cells (P<0.001). The expression of miR-215 in HXO-Rb44 cells was significantly higher than that in Y79 cells (P<0.001). The expression of miR-215 was statistically different from the degree of differentiation and nerve infiltration (P<0.05). The expression of Rb1 in cancer tissues was significantly lower than that in adjacent tissues (P<0.001), the expression of APRE-19 was significantly higher than that in Y79 and HXO-Rb44 cells (P<0.001), and the expression of Rb1 in HXO-Rb44 cells was significantly higher than that in Y79 cells (P<0.05). There was a negative correlation between miR-215 and Rb1 in the tissues of patients, and Rb1 expression decreased with the increase of miR-215 (r=-0.576, P<0.001). Conclusion: miR‑215 is highly expressed in Rb cell lines, and is related to the clinicopathological features of this disease.

Mutations in tumor suppressor gene, FBXW7, are associated with carboplatin resistance in endometrial cancer cell lines

2015 ◽  
Vol 139 (1) ◽  
pp. 194 ◽  
Author(s):  
Alexandre Buckley de Meritens ◽  
Ayesha Joshi ◽  
Christopher Miller ◽  
Lora Hedrick Ellenson ◽  
Divya Gupta
Keyword(s):  
Endometrial Cancer ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Suppressor Gene ◽  
Endometrial Cancer Cell

scholarly journals Nkx2.5 Functions as a Conditional Tumor Suppressor Gene in Colorectal Cancer Cells via Acting as a Transcriptional Coactivator in p53-Mediated p21 Expression

2021 ◽  
Vol 11 ◽  
Author(s):  
Huili Li ◽  
Jiliang Wang ◽  
Kun Huang ◽  
Tao Zhang ◽  
Lu Gao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Expression Pattern ◽  
Cell Lines ◽  
Suppressor Gene ◽  
Transcriptional Coactivator ◽  
Wild Type ◽  
Mutational Status ◽  
Sw480 Cells

NK2 homeobox 5 (Nkx2.5), a homeobox-containing transcription factor, is associated with a spectrum of congenital heart diseases. Recently, Nkx2.5 was also found to be differentially expressed in several kinds of tumors. In colorectal cancer (CRC) tissue and cells, hypermethylation of Nkx2.5 was observed. However, the roles of Nkx2.5 in CRC cells have not been fully elucidated. In the present study, we assessed the relationship between Nkx2.5 and CRC by analyzing the expression pattern of Nkx2.5 in CRC samples and the adjacent normal colonic mucosa (NCM) samples, as well as in CRC cell lines. We found higher expression of Nkx2.5 in CRC compared with NCM samples. CRC cell lines with poorer differentiation also had higher expression of Nkx2.5. Although this expression pattern makes Nkx2.5 seem like an oncogene, in vitro and in vivo tumor suppressive effects of Nkx2.5 were detected in HCT116 cells by establishing Nkx2.5-overexpressed CRC cells. However, Nkx2.5 overexpression was incapacitated in SW480 cells. To further assess the mechanism, different expression levels and mutational status of p53 were observed in HCT116 and SW480 cells. The expression of p21WAF1/CIP1, a downstream antitumor effector of p53, in CRC cells depends on both expression level and mutational status of p53. Overexpressed Nkx2.5 could elevate the expression of p21WAF1/CIP1 only in CRC cells with wild-type p53 (HCT116), rather than in CRC cells with mutated p53 (SW480). Mechanistically, Nkx2.5 could interact with p53 and increase the transcription of p21WAF1/CIP1 without affecting the expression of p53. In conclusion, our findings demonstrate that Nkx2.5 could act as a conditional tumor suppressor gene in CRC cells with respect to the mutational status of p53. The tumor suppressive effect of Nkx2.5 could be mediated by its role as a transcriptional coactivator in wild-type p53-mediated p21WAF1/CIP1 expression.

scholarly journals Functional evidence for a second tumor suppressor gene on human chromosome 17

1994 ◽  
Vol 14 (1) ◽  
pp. 534-542
Author(s):  
P Chen ◽  
N Ellmore ◽  
B E Weissman
Keyword(s):  
Tumor Suppressor ◽  
Cell Line ◽  
Tumor Suppressor Gene ◽  
Cell Lines ◽  
Suppressor Gene ◽  
Chromosome 17 ◽  
Hybrid Cells ◽  
Tumorigenic Potential ◽  
Normal Human ◽  
Second Tumor

The development and progression of human tumors often involves inactivation of tumor suppressor gene function. Observations that specific chromosome deletions correlate with distinct groups of cancer suggest that some types of tumors may share common defective tumor suppressor genes. In support of this notion, our initial studies showed that four human carcinoma cell lines belong to the same complementation group for tumorigenic potential. In this investigation, we have extended these studies to six human soft tissue sarcoma cell lines. Our data showed that hybrid cells between a peripheral neuroepithelioma (PNET) cell line and normal human fibroblasts or HeLa cells were nontumorigenic. However, hybrid cells between the PNET cell line and five other soft tissue sarcoma cell lines remained highly tumorigenic, suggesting at least one common genetic defect in the control of tumorigenic potential in these cells. To determine the location of this common tumor suppressor gene, we examined biochemical and molecular polymorphic markers in matched pairs of tumorigenic and nontumorigenic hybrid cells between the PNET cell line and a normal human fibroblast. The data showed that loss of the fibroblast-derived chromosome 17 correlated with the conversion from nontumorigenic to tumorigenic cells. Transfer of two different chromosome 17s containing a mutant form of the p53 gene into the PNET cell line caused suppression of tumorigenic potential, implying the presence of a second tumor suppressor gene on chromosome 17.

scholarly journals Alterations of the p53 tumor suppressor gene in diffuse large cell lymphomas with translocations of the c-MYC and BCL-2 proto-oncogenes

Blood ◽  
1994 ◽  
Vol 83 (1) ◽  
pp. 191-198 ◽  
Author(s):  
MM Farrugia ◽  
LJ Duan ◽  
MD Reis ◽  
BY Ngan ◽  
NL Berinstein
Keyword(s):  
Tumor Suppressor ◽  
Cell Line ◽  
Tumor Suppressor Gene ◽  
Cell Lines ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Suppressor Gene ◽  
Diffuse Large Cell Lymphoma ◽  
P53 Tumor Suppressor Gene ◽  
Large Cell Lymphoma

Abstract Diffuse large cell lymphomas are aggressive tumors of B-cell origin. In some cases they arise from low-grade follicular lymphomas carrying the t(14;18) translocation, an event that leads to the overexpression of the BCL-2 gene product. More frequently, however, they lack the t(14;18) translocation. Rearrangements of the c-MYC proto-oncogene and mutations of the p53 tumor suppressor gene have also been documented in these lymphomas. This study examines the extent to which alterations in the BCL-2, c-MYC, and p53 genes co-exist within individual lymphomas. Eight diffuse large cell lymphoma cell lines and 11 diffuse large cell lymphoma tumors were assessed for genetic alterations in these three genes. Our results indicate that there is a heterogeneity in the oncogene/suppressor gene profile among diffuse large cell lymphomas. Two cell lines and one tumor carried alterations in all three genes, one cell line carried alterations of c-MYC and p53, and one primary tumor and one cell line carried p53 mutations and the t(14;18). Single alterations of BCL-2 and p53 were also observed. Another cell line had no alterations in any of these genes. The heterogeneity indicates that varied mechanisms may be involved in the generation of diffuse large cell lymphomas.

Mutations of the Tumor Suppressor Gene SOCS-1 in Classical Hodgkin Lymphoma Are Frequent and Associated with Nuclear Phospho-STAT5 Accumulation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 19-19 ◽  
Author(s):  
Marc A. Weniger ◽  
Ingo Melzner ◽  
Christiane K. Menz ◽  
Silke Wegener ◽  
Alexandra J. Bucur ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Tumor Suppressor Gene ◽  
Cell Lines ◽  
B Cell Lymphoma ◽  
Suppressor Gene ◽  
Cytokine Signaling ◽  
Sequencing Analysis ◽  
Classical Hodgkin Lymphoma

Abstract The suppressors of cytokine signaling (SOCS) are critically involved in the regulation of cellular proliferation, survival, and apoptosis via cytokine-induced JAK/STAT signaling. SOCS-1 silencing by aberrant DNA methylation contributes to oncogenesis in various B-cell neoplasias and carcinomas. Recently, we showed an alternative loss of SOCS-1 function due to deleterious SOCS-1 mutations in a major subset of primary mediastinal B-cell lymphoma (PMBL) and in the PMBL line MedB-1, and a biallelic SOCS-1 deletion in PMBL line Karpas1106P (BLOOD, 105, 2535–42, 2005). For both cell lines our previous data demonstrated retarded JAK2 degradation and sustained phospho-JAK2 action leading to enhanced DNA binding of phospho-STAT5. Here we analysed SOCS-1 in laser-microdissected Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL). We detected SOCS-1 mutations in HRS cells of eight of 19 cHL samples and in three of five Hodgkin lymphoma (HL)-derived cell lines by sequencing analysis. Moreover, we found a significant association between mutated SOCS-1 of isolated HRS cells and nuclear phospho-STAT5 accumulation in HRS cells of cHL tumor tissue (p<0.01). Collectively, these findings support the concept that PMBL and cHL share many overlapping features, and that defective tumor suppressor gene SOCS-1 triggers an oncogenic pathway operative in both lymphomas.

Downregulation of a Candidate Myeloid Tumor Suppressor Gene Isolated from 7q21 Induces Abnormal Mitosis Due to Insufficient Centrosome Maturation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2638-2638
Author(s):  
Hiroya Asou ◽  
Hirotaka Matsui ◽  
Yuko Ozaki ◽  
Akiko Nagamachi ◽  
Daisuke Aki ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Cell Lines ◽  
Myeloid Leukemia ◽  
Leukemia Cell ◽  
Suppressor Gene ◽  
Monosomy 7 ◽  
Leukemia Cell Lines ◽  
Abnormal Mitosis ◽  
Tankyrase 1

Abstract To isolate myeloid tumor suppressor gene(s) in 7q, we searched microdeletions in a region spanning 21.7 Mb within 7q21.2–7q31.1 using a microarray-based CGH system. By investigation of 21 childhood myeloid leukemia patients with normal karyotype, we identified a common microdeletion cluster spanning approximately 120 Kb in the 7q21.3 subband. Eight (38%) patients shared this microdeletion, which was not detected in normal individuals. Real-time quantitative PCR revealed that this region is also deleted in 9 (29%) out of 31 adult RAEB and AML patients. Database search revealed that this region contains three hypothetical genes. Among them, we chose one previously uncharacterized gene for further investigation and named Miki (mitotic kinetics regulator) for the function of its gene product, described below. Immunoblot analysis revealed high levels of Miki expression in most lymphoid leukemia cell lines, while half of myeloid leukemia cell lines expressed Miki at reduced levels. In six leukemia lines carrying monosomy 7, expression levels were generally low. Miki co-localized with the Golgi apparatus in the interphase and with centrosomes and spindles in the mitotic phase. To test the function of Miki, we used si-RNAs to downregulate Miki expression in HeLa and K562 cells, both of which show basically normal metaphase and nuclear morphology. Cells expressing Miki at reduced levels showed insufficient maturation and disturbed positioning of centrosomes, resulting in unorganized spindles including loss of spindle tension, curled and fragile spindles, or even completely disturbed spindle formation. Time-lapse observation revealed prometaphase and/or metaphase delay with unaligned or even totally scattered chromosomes in prometaphase in virtually all cells in the mitotic phase. As a result, cells underwent pre-anaphase arrest and exited mitosis in the absence of chromosome segregation or terminated mitosis by cell death. In the interphase, there were many cells with chromatid bridges and/or bi- or tri-nuclear or even multinuclear cells with micronuclei that resembled pathological cells routinely observed in the bone marrow pictures of MDS patients. Interestingly, myeloid cell lines with low Miki expression, including those with monosomy 7, generally showed abnormal mitosis such as scattered chromosomes and abnormal nuclear morphologies (multi-nuclear cells with small nuclei) at higher frequency than cell lines expressing Miki at high levels. Moreover, induction of Miki restores normal mitosis in leukemia cells with monosomy 7. Miki was poly(ADP-ribosyl)ated (PARsylated) in late G2 to M phase by tankyrase-1, one of PAR polymerase (PARP), and tankyrase-1 activity was required for the binding of Miki to spindles and centrosomes. These data suggest that loss of Miki gene contributes to the development and progression of MDS by disturbing mitosis.

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