scholarly journals FXR1 regulates transcription and is required for growth of human cancer cells with TP53/FXR2 homozygous deletion

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Yichao Fan ◽  
Jiao Yue ◽  
Mengtao Xiao ◽  
Han Han-Zhang ◽  
Yao Vickie Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cancer Cells ◽  
Rna Binding ◽  
Cell Transformation ◽  
Human Cancer ◽  
Homozygous Deletion ◽  
Gene Promoters ◽  
Neighboring Gene ◽  
Human Cancer Cells ◽  
Human Cancers

Tumor suppressor p53 prevents cell transformation by inducing apoptosis and other responses. Homozygous TP53 deletion occurs in various types of human cancers for which no therapeutic strategies have yet been reported. TCGA database analysis shows that the TP53 homozygous deletion locus mostly exhibits co-deletion of the neighboring gene FXR2, which belongs to the Fragile X gene family. Here, we demonstrate that inhibition of the remaining family member FXR1 selectively blocks cell proliferation in human cancer cells containing homozygous deletion of both TP53 and FXR2 in a collateral lethality manner. Mechanistically, in addition to its RNA-binding function, FXR1 recruits transcription factor STAT1 or STAT3 to gene promoters at the chromatin interface and regulates transcription thus, at least partially, mediating cell proliferation. Our study anticipates that inhibition of FXR1 is a potential therapeutic approach to targeting human cancers harboring TP53 homozygous deletion.

scholarly journals DOX-Vit D, a Novel Doxorubicin Delivery Approach, Inhibits Human Osteosarcoma Cell Proliferation by Inducing Apoptosis While Inhibiting Akt and mTOR Signaling Pathways

Pharmaceutics ◽  
2018 ◽  
Vol 10 (3) ◽  
pp. 144 ◽  
Author(s):  
Zaid Maayah ◽  
Ti Zhang ◽  
Marcus Forrest ◽  
Samaa Alrushaid ◽  
Michael Doschak ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Human Cancer ◽  
Death Receptor ◽  
Osteosarcoma Cell ◽  
Acquired Drug Resistance ◽  
Human Cancer Cells ◽  
Mg63 Cells ◽  
Delivery Approach

Doxorubicin (DOX) is a very potent and effective anticancer agent. However, the effectiveness of DOX in osteosarcoma is usually limited by the acquired drug resistance. Recently, Vitamin D (Vit-D) was shown to suppress the growth of many human cancer cells. Taken together, we synthesized DOX-Vit D by conjugating Vit-D to DOX in order to increase the delivery of DOX into cancer cells and mitigate the chemoresistance associated with DOX. For this purpose, MG63 cells were treated with 10 µM DOX or DOX-Vit D for 24 h. Thereafter, MTT, real-time PCR and western blot analysis were used to determine cell proliferation, genes and proteins expression, respectively. Our results showed that DOX-Vit D, but not DOX, significantly elicited an apoptotic signal in MG63 cells as evidenced by induction of death receptor, Caspase-3 and BCLxs genes. Mechanistically, the DOX-Vit D-induced apoptogens were credited to the activation of p-JNK and p-p38 signaling pathway and the inhibition of proliferative proteins, p-Akt and p-mTOR. Our findings propose that DOX-Vit D suppressed the growth of MG63 cells by inducing apoptosis while inhibiting cell survival and proliferative signaling pathways. DOX-Vit D may serve as a novel drug delivery approach to potentiate the delivery of DOX into cancer cells.

scholarly journals The Dynamin Inhibitors MiTMAB and OcTMAB Induce Cytokinesis Failure and Inhibit Cell Proliferation in Human Cancer Cells

2010 ◽  
Vol 9 (7) ◽  
pp. 1995-2006 ◽  
Author(s):  
Sanket Joshi ◽  
Swetha Perera ◽  
Jayne Gilbert ◽  
Charlotte M. Smith ◽  
Anna Mariana ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cancer Cells ◽  
Human Cancer ◽  
Human Cancer Cells ◽  
Inhibit Cell Proliferation

Opioid growth factor-opioid growth factor receptor axis is a physiological determinant of cell proliferation in diverse human cancers

2009 ◽  
Vol 297 (4) ◽  
pp. R1154-R1161 ◽  
Author(s):  
Ian S. Zagon ◽  
Renee N. Donahue ◽  
Patricia J. McLaughlin
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Cancer Cells ◽  
Human Cancer ◽  
Growth Factor Receptor ◽  
Cell Number ◽  
Treatment Modalities ◽  
Human Cancer Cell Lines ◽  
Human Cancer Cells ◽  
Opioid Growth Factor

The opioid growth factor (OGF) regulates cell proliferation of human cancer cells through the cyclin-dependent kinase inhibitory pathway, with mediation of this action by the OGF receptor (OGFr). The ubiquity of the OGF-OGFr axis in human cancer is unknown. We used 31 human cancer cell lines, representative of more than 90% of neoplasias occurring in humans, and found that OGF and OGFr were detected in the cytoplasm and nucleus by immunohistochemistry. The addition of OGF to cultures depressed cell number up to 41%, whereas naltrexone (NTX) increased cell proliferation by up to 44%, a total of 85% in the modulating capacity for the OGF-OGFr axis. Neutralization of OGF by specific antibodies led to a marked increase in cell number. Knockdown of OGFr by OGFr-siRNA resulted in a significant increase in the number of cells, even in the face of the addition of exogenous OGF. The cultures to which NTX was added and subjected to OGFr-siRNA were similar to those with OGF-siRNA alone. The OGF-OGFr axis, a physiological determinant of cell-proliferative activity, is a ubiquitous feature of human cancer cells. The identification of this native biological system in neoplasia may be important in understanding the pathophysiology of neoplasia, and in designing treatment modalities that utilize the body's own chemistry.

scholarly journals Functional characterization of miR-708 microRNA in telomerase positive and negative human cancer cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zeenia Kaul ◽  
Caroline T. Y. Cheung ◽  
Priyanshu Bhargava ◽  
Anissa Notifa Sari ◽  
Yue Yu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cancer Cells ◽  
Human Cancer ◽  
Functional Characterization ◽  
Array Analysis ◽  
Mirna Microarray ◽  
Human Cancer Cells ◽  
Large Panel ◽  
Proliferation Regulation

AbstractActivation of a telomere length maintenance mechanism (TMM), including telomerase and alternative lengthening of telomeres (ALT), is essential for replicative immortality of tumor cells, although its regulatory mechanisms are incompletely understood. We conducted a microRNA (miRNA) microarray analysis on isogenic telomerase positive (TEP) and ALT cancer cell lines. Amongst nine miRNAs that showed difference in their expression in TEP and ALT cancer cells in array analysis, miR-708 was selected for further analysis since it was consistently highly expressed in a large panel of ALT cells. miR-708 in TEP and ALT cancer cells was not correlated with C-circle levels, an established feature of ALT cells. Its overexpression induced suppression of cell migration, invasion, and angiogenesis in both TEP and ALT cells, although cell proliferation was inhibited only in TEP cells suggesting that ALT cells may have acquired the ability to escape inhibition of cell proliferation by sustained miR-708 overexpression. Further, cell proliferation regulation in TEP cells by miR708 appears to be through the CARF-p53 pathway. We demonstrate here that miR-708 (i) is the first miRNA shown to be differentially regulated in TEP and ALT cancer cells, (ii) possesses tumor suppressor function, and (iii) deregulates CARF and p21WAF1-mediated signaling to limit proliferation in TEP cells.

Cell Proliferation of Cultured Human Cancer Cells are Affected by the Elevated Tumor Pressures that Exist In Vivo

2005 ◽  
Vol 33 (9) ◽  
pp. 1270-1280 ◽  
Author(s):  
Gene R. DiResta ◽  
Saminathan S. Nathan ◽  
Mark W. Manoso ◽  
Jorge Casas-Ganem ◽  
Chris Wyatt ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cancer Cells ◽  
Human Cancer ◽  
Human Cancer Cells ◽  
Cultured Human Cancer Cells
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