scholarly journals CDK13-Mediated Cell Cycle Disorder Promotes Tumorigenesis of High HMGA2 Expression Gastric Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Zhouying Wu ◽  
Min Wang ◽  
Feng Li ◽  
Feng Wang ◽  
Jianchao Jia ◽  
...  

The inhibitor of CDK4/6 has been clinically used for treating certain types of cancer which are characterized by G0/G1 acceleration induced by the CDK4/6-RB1 pathway. On the contrary, the cell cycle–related molecules are abnormal in over 50% of the patients with gastric cancer (GC), but the efficiency of inhibiting CDK4/6 does not work well as it is expected. In our study, we found HMGA2 promotes GC through accelerating the S–G2/M phase transition, instead of G0/G1. We also found CDK13 is the direct target gene of HMGA2. Importantly, we analyzed 200 pairs of GC and the adjacent tissue and proved the positive relation between HMGA2 and CDK13; moreover, high expression of both genes predicts a poorer prognosis than the expression of single gene does. We explored the effect of the novel CDK12/13 inhibiting agent, SR-4835, on high HMGA2 expression GC and found inhibition of both genes jointly could reach a satisfied result. Therefore, we suggest that inhibition of CDK13 and HMGA2 simultaneously could be an effective strategy for high HMGA2 expression GC. To detect the expression of both genes simultaneously and individually could be of benefit to predict prognosis for GC.

2019 ◽  
Vol 400 (8) ◽  
pp. 1079-1086 ◽  
Author(s):  
Su’e Chang ◽  
Zhengchao Gao ◽  
Yang Yang ◽  
Kang He ◽  
Xiaofei Wang ◽  
...  

Abstract Vitamin D3 is known to have anticancer actions by affecting tumorigenesis including the cell cycle and cell apoptosis in gastric cancer (GC) cells; the genes including microRNAs (miRNAs) regulated by vitamin D3 signaling remain discovered. miR-99b-3p, the tumor suppressor gene, is not only decreased in GC tissues, but is also induced by vitamin D3 through the vitamin D receptor (VDR) binding on the promoter domain of miR-99b. Further study indicates that miR-99b-3p inhibits cell viability and induces cell arrest in the S-phase in GC cells, the direct target gene of miR-99b-3p is verified to be HoxD3, which is also overexpressed in GC cell lines. Overall, our results show that miR-99b-3p mediates the antiproliferative of vitamin D3 in GC cells and might hold promise for prognosis and therapeutic strategies for GC treatment.


2013 ◽  
Vol 133 (2) ◽  
pp. 335-345 ◽  
Author(s):  
Joost L. Boormans ◽  
Hanneke Korsten ◽  
Angelique J.C. Ziel-van der Made ◽  
Geert J.L.H. van Leenders ◽  
Carola V. de Vos ◽  
...  

2014 ◽  
Vol 458 (1) ◽  
pp. 171-183 ◽  
Author(s):  
Jing Chen ◽  
Xiao-Bo Li ◽  
Rui Su ◽  
Li Song ◽  
Fang Wang ◽  
...  

The present study demonstrated that ZNF16 (HZF1) plays an important role in erythroid and megakaryocytic differentiation of human haematopoietic stem/progenitor cells, identified and validated c-KIT as a direct target gene of ZNF16, and demonstrated that ZNF16 functions via its regulation on the c-Kit/c-Raf/MEK/ERK/c-Jun/HEY1/GATA1 cascade.


2020 ◽  
Author(s):  
Yi Gao ◽  
Yanfeng Wang ◽  
Xiaofei Wang ◽  
Changan Zhao ◽  
Fenghui Wang ◽  
...  

Abstract Background: In recent years, many microRNAs(miRNAs) involved in cancer progression. The aberrant expression of miR-335-5p in tumorigenesis has been demonstrated. The present study aimed to investigate the molecular mechanisms underlying miR-335-5p- regulated MAPK10 expression in human gastric cancer(GC).Methods: The quantitative real-time PCR was used to study the level of miR-335-5p expression in gastric cancer cell lines and tissues. Subsequently, the MTT and cloning formation assays were used to detect cell proliferation, while transwell and wound-healing assays were used to identify invasion and migration of the gastric cancer cells. The correlation between the miR-335-5p and the cell cycle-related target gene mitogen‑activated protein kinase 10 (MAPK10) in gastric cancer was analyzed based on the website. In addition, the target gene of miR-335-5p was detected by luciferase reporter assay, qRT-PCR, and western blotting.Results: The miR-335-5p level was down-regulated in GC tissues and cell lines. Furthermore, miR-335-5p inhibited proliferation, migration of gastric cancer cells, and induced apoptosis. During the G1/S phase, miR-335-5p arrested the cycle of gastric cancer cells in vitro. The correlation between the miR-335-5p and the cell cycle-related target gene MAPK10 in GC was analyzed, MAPK10 was directly targeted by the miR-335-5p.Conclusion: These data suggested that miR-335-5p acts as a tumor suppressor, and go through the MAPK10 to inhibit the GC progression.


2011 ◽  
Vol 287 (8) ◽  
pp. 5366-5378 ◽  
Author(s):  
Bénédicte Foveau ◽  
Gaylor Boulay ◽  
Sébastien Pinte ◽  
Capucine Van Rechem ◽  
Brian R. Rood ◽  
...  

Author(s):  
Lihua Jiang ◽  
Wenchuan Yang ◽  
Weishi Bian ◽  
Hailin Yang ◽  
Xia Wu ◽  
...  

The dysregulation of microRNAs (miRNAs) plays an important function in the onset and progression of gastric cancer (GC). In addition, aberrantly expressed miRNAs affect the chemosensitivity of GC cells to chemotherapeutic drugs. Hence, miRNA-based targeted therapy might be applied to treat patients with GC exhibiting chemotherapeutic resistance. In this study, miRNA-623 (miR-623) expression was downregulated in GC tissues and cell lines. Functional analysis showed that the restored miR-623 expression could inhibit the proliferation of GC cells and enhance their chemosensitivity to 5-FU via the cell apoptosis pathway. Cyclin D1 (CCND1) was identified as a direct target gene of miR-623 in GC. The overexpressed CCND1 in GC tissues was negatively correlated with miR-623 level. The recovered CCND1 expression counteracted the effects of miR-623 on GC cell proliferation, chemosensitivity, and 5-FU-induced apoptosis. Thus, our results suggest that miR-623 might function as a tumor suppressor in GC and could be a promising therapeutic target for patients with GC, especially those with chemotherapeutic resistance.


2009 ◽  
Vol 284 (31) ◽  
pp. 20927-20935 ◽  
Author(s):  
Capucine Van Rechem ◽  
Brian R. Rood ◽  
Majid Touka ◽  
Sébastien Pinte ◽  
Mathias Jenal ◽  
...  

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