scholarly journals ISLET1-Dependent β-Catenin/Hedgehog Signaling Is Required for Outgrowth of the Lower Jaw

2017 ◽  
Vol 37 (8) ◽  
Author(s):  
Feixue Li ◽  
Guoquan Fu ◽  
Ying Liu ◽  
Xiaoping Miao ◽  
Yan Li ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Transcription Factor ◽  
Transcriptional Regulation ◽  
Cell Survival ◽  
Sonic Hedgehog ◽  
Cell Apoptosis ◽  
Hedgehog Signaling ◽  
Mesenchymal Cell ◽  
Functional Roles ◽  
Lower Jaw

ABSTRACT Mandibular patterning information initially resides in the epithelium during development. However, how transcriptional regulation of epithelium-derived signaling controls morphogenesis of the mandible remains elusive. Using Shh Cre to target the mandibular epithelium, we ablated transcription factor Islet1, resulting in a distally truncated mandible via unbalanced cell apoptosis and decreased cell proliferation in the distal mesenchyme. Loss of Islet1 caused a lack of cartilage at the distal tip, leading the fusion of two growing mandibular elements surrounding the rostral process of Meckel's cartilage. Loss of Islet1 results in dysregulation of mesenchymal genes important for morphogenesis of the mandibular arch. We revealed that Islet1 is required for the activation of epithelial β-catenin signaling via repression of Wnt antagonists. Reactivation of β-catenin in the epithelium of the Islet1 mutant rescued mandibular morphogenesis through sonic hedgehog (SHH) signaling to the mesenchyme. Furthermore, overexpression of a transgenic hedgehog ligand in the epithelium also partially restored outgrowth of the mandible. These data reveal functional roles for an ISLET1-dependent network integrating β-catenin/SHH signals in mesenchymal cell survival and outgrowth of the mandible during development.

scholarly journals A critical role of autocrine sonic hedgehog signaling in human CD138+ myeloma cell survival and drug resistance

Blood ◽  
2014 ◽  
Vol 124 (13) ◽  
pp. 2061-2071 ◽  
Author(s):  
Zhiqiang Liu ◽  
Jingda Xu ◽  
Jin He ◽  
Yuhuan Zheng ◽  
Haiyan Li ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cell Survival ◽  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
Critical Role ◽  
Myeloma Cell ◽  
Sonic Hedgehog Signaling ◽  
Key Points

Key Points CD138+ MM cells are a major source of SHH. Autocrine SHH enhances MM drug resistance.

scholarly journals Up-Regulated ATF4 Expression Increases Cell Sensitivity to Apoptosis in Response to Radiation

2017 ◽  
Vol 41 (2) ◽  
pp. 784-794 ◽  
Author(s):  
Ying Zong ◽  
Shijie Feng ◽  
Jinwei Cheng ◽  
Chenlin Yu ◽  
Guocai Lu
Keyword(s):  
Cell Proliferation ◽  
Transcription Factor ◽  
Cell Apoptosis ◽  
Hek293 Cells ◽  
Cell Counting ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Over Expression ◽  
Radiation Induced ◽  
Activating Transcription Factor

Background/Aims: Activating transcription factor 4 (ATF4) is a member of the activating transcription factor family which regulates the expression of genes involved in amino acid metabolism, redox homeostasis and ER stress responses. ATF4 is also over-expressed in human solid tumors, although its effect on responsiveness to radiation is largely unexplored. Methods: Real-time PCR was used to detect ATF4 mRNA levels in cells treated with different doses of 60Coγ radiation. Cell viability was assayed using a cell counting kit. The cell cycle was analyzed using flow cytometry, and cell apoptosis was assayed using Annexin V-PI double labeling. Small interfering RNA (siRNA) against ATF4 was transfected into ECV304 cells using Lipofectamine 2000. An ATF4 over-expression plasmid (p-ATF4-CGN) was transfected into HEK293 cells that endogenously expressed low levels of ATF4. The levels of intracellular reactive oxygen species (ROS) were measured using CM-H2DCFDA as a probe. Results: ATF4 mRNA and protein expression levels were higher after radiation and increased in a dose- and time-dependent manner in AHH1 lymphoblast cells (P < 0.05). An increase in ATF4 levels was also observed after radiation in primary murine spleen cells, human endothelial ECV304 cells, human liver LO2 cells, breast cancer MCF7 cells, and human hepatocellular carcinoma HEPG2 cells. No change was observed in human embryonic kidney 293 (HEK293) cells. Over-expressing ATF4 in HEK293 cells inhibited cell proliferation, increased cell apoptosis and significantly increased the proportion of cells in G1 phase. Conversely, when ATF4 expression was knocked down using siRNA in ECV304 cells, it protected the cells from radiation-induced apoptosis. These findings suggest that ATF4 may play a role in radiation-induced cell killing by inhibiting cell proliferation and promoting cell apoptosis. Conclusions: In this study, we found that radiation up-regulated the expression of ATF4. We used ATF4 knockdown and over-expression systems to show that ATF4 may play a role in radiation-induced cellular apoptosis.

scholarly journals Forkhead Transcription Factor FKHR-L1 Modulates Cytokine-Dependent Transcriptional Regulation of p27KIP1

2000 ◽  
Vol 20 (24) ◽  
pp. 9138-9148 ◽  
Author(s):  
Pascale F. Dijkers ◽  
Rene H. Medema ◽  
Cornelieke Pals ◽  
Lolita Banerji ◽  
N. Shaun B. Thomas ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcriptional Regulation ◽  
Cell Survival ◽  
Kinase Inhibitor ◽  
Ectopic Expression ◽  
Dependent Manner ◽  
Forkhead Transcription Factor ◽  
Protein Levels ◽  
Macrophage Colony ◽  
Null Mutant Mice

ABSTRACT Interleukin-3 (IL-3), IL-5, and granulocyte-macrophage colony-stimulating factor regulate the survival, proliferation, and differentiation of hematopoietic lineages. Phosphatidylinositol 3-kinase (PI3K) has been implicated in the regulation of these processes. Here we investigate the molecular mechanism by which PI3K regulates cytokine-mediated proliferation and survival in the murine pre-B-cell line Ba/F3. IL-3 was found to repress the expression of the cyclin-dependent kinase inhibitor p27KIP1 through activation of PI3K, and this occurs at the level of transcription. This transcriptional regulation occurs through modulation of the forkhead transcription factor FKHR-L1, and IL-3 inhibited FKHR-L1 activity in a PI3K-dependent manner. We have generated Ba/F3 cell lines expressing a tamoxifen-inducible active FKHR-L1 mutant [FKHR-L1(A3):ER*]. Tamoxifen-mediated activation of FKHR-L1(A3):ER* resulted in a striking increase in p27KIP1 promoter activity and mRNA and protein levels as well as induction of the apoptotic program. The level of p27KIP1 appears to be critical in the regulation of cell survival since mere ectopic expression of p27KIP1 was sufficient to induce Ba/F3 apoptosis. Moreover, cell survival was increased in cytokine-starved bone marrow-derived stem cells from p27KIP1 null-mutant mice compared to that in cells from wild-type mice. Taken together, these observations indicate that inhibition of p27KIP1transcription through PI3K-induced FKHR-L1 phosphorylation provides a novel mechanism of regulating cytokine-mediated survival and proliferation.

scholarly journals Sonic Hedgehog Signaling Promotes Peri-Lesion Cell Proliferation and Functional Improvement after Cortical Contusion Injury

2021 ◽  
Vol 2 (1) ◽  
pp. 27-38
Author(s):  
Ashley K. Pringle ◽  
Elshadaie Solomon ◽  
Benjamin J. Coles ◽  
Brandon R. Desousa ◽  
Anan Shtaya ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
Functional Improvement ◽  
Sonic Hedgehog Signaling ◽  
Contusion Injury ◽  
Cortical Contusion

Chinese Herb Resveratrol Inhibits Renal Pelvic Cancer Cell Proliferation via Regulating miR-30a-5p

2021 ◽  
Vol 15 (2) ◽  
pp. 253-259
Author(s):  
Zunwei Zhu ◽  
Jinggong Wu ◽  
Lieyu Xu ◽  
Yong Wan ◽  
Haichao Chao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Survival ◽  
Renal Pelvis ◽  
Cell Apoptosis ◽  
Target Gene ◽  
Chinese Herb ◽  
Cancer Cell Proliferation ◽  
Pelvic Cancer ◽  
Renal Pelvic Cancer

Renal pelvis cancer (RPC) is rare with unclear pathogenesis. Resveratrol (RSV) also plays a beneficial role in preventing chronic diseases related to inflammation. But its effect on RPC cells has not been reported. RPC cells were cultured and treated with resveratrol for 48 hours followed by analysis of cell proliferation, apoptosis and cell cycle, and miR-30a-5p expression. The expression of miR-30a-5p effects proliferation, apoptosis and cell cycle was also assessed. After treatment, RPC cells showed upregulated miR-30a-5p, decreased cell survival and enhanced cell apoptosis rate compared with abnormal cell cycle (P < 0.05), and the effect was more significant with the increase in concentration (P < 0.05). The miR-30a-5p target gene is AVEN. miR-30a-5p downregulation can reverse its effect on RPC cells (P < 0.05). Resveratrol treatment on RPC cells can upregulate miR-30a-5p, inhibite cell proliferation, promotes apoptosis, and changes cell cycle.

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.

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