UPF1 promotes chemoresistance to oxaliplatin through regulation of TOP2A activity and maintenance of stemness in colorectal cancer

Zhu, Congcong; Zhang, Long; Zhao, Senlin; Dai, Weixing; Xu, Yun; Zhang, Yuqin; Zheng, Hua; Sheng, Weiqi; Xu, Ye

doi:10.1038/s41419-021-03798-2

Cited by 20 publications

(15 citation statements)

References 56 publications

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“…In various types of tumors, including HCC, TOP2A shows huge expression differences. TOP2A expression is correlated with tumor resistance [22][23][24]. In 2019, Peng et al [25] found that a small group of malignant cells from pancreatic ductal adenocarcinoma sample expressed MKI67, TOP2A, and CCNB1, and these cells showed a high degree of malignancy to promote tumor progression.…”

Section: Discussionmentioning

confidence: 99%

DNA Topoisomerase II-α Regulated by miR-22-5p Promotes Hepatocellular Carcinoma Invasion and Migration through the Hippo Pathway

Zhao

Chen

Song

et al. 2022

Oxidative Medicine and Cellular Longevity

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DNA topoisomerases (TOPs) are dysregulated in various types of cancer. However, how TOP II-alpha (TOP2A) contributes to hepatocellular carcinoma (HCC) progression remains elusive. Cohort analysis revealed that the increased expression of TOP2A was associated with poor clinical outcomes and TOP2A was significantly upregulated in HCC tissues and cell lines. In vitro, TOP2A expression level is related to cell invasion and migration, which may be due to the alteration of epithelial-mesenchymal transition by the TOP2A. Moreover, we used verteporfin (a Hippo inhibitor) to test how the Hippo pathway promotes the effect of TOP2A on the HCC phenotype and found that TOP2A induces tumor progression through the Hippo pathway. Finally, miR-22-5p inhibited tumor progression by sponging TOP2A.

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Section: Discussionmentioning

confidence: 99%

DNA Topoisomerase II-α Regulated by miR-22-5p Promotes Hepatocellular Carcinoma Invasion and Migration through the Hippo Pathway

Zhao

Chen

Song

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…UPF1 is an RNA-binding protein that can undergo NMD; staufen-mediated mRNA decay; replication-dependent histone mRNA decay; glucocorticoid receptor-mediated mRNA decay; regnase 1-mediated mRNA decay; and tudor-staphylococcal/micrococcal-like nuclease-mediated microRNA decay. Moreover, UPF1 can regulate the malignant behavior of tumors [ 45 , 46 ], maintain stem cell stemness, and inhibit differentiation [ 23 , 24 , 47 ]. The expression of UPF1 in endometrial cancer tissues is higher than that in adjacent tissues, which can promote the growth and progression of endometrial cancer, increase the activity of the mTOR pathway, inhibit autophagy [ 48 ], and promote the malignant behavior and stemness of ECSCs [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

“…The overexpression of UPF1 in neuronal stem cells favors cell proliferation and maintains a stem cell-like state [ 23 ]. Moreover, UPF1 expression is elevated in rectal cancer and maintains rectal cancer stem cell stemness [ 24 ]. In studies of endometrial cancer, UPF1 expression has been found to be elevated and promotes the stemness of ECSCs [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

PVT1/miR-136/Sox2/UPF1 axis regulates the malignant phenotypes of endometrial cancer stem cells

Kong

Cong

et al. 2023

Cell Death Dis

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Tumor stem cells (TSCs) are thought to contribute to the progression and maintenance of cancer. Previous studies have suggested that plasmacytoma variant translocation 1 (PVT1) has a tumor-promoting effect on endometrial cancer; however, its mechanism of action in endometrial cancer stem cells (ECSCs) is unknown. Here, we found that PVT1 was highly expressed in endometrial cancers and ECSCs, correlated with poor patient prognosis, promoted the malignant behavior and the stemness of endometrial cancer cells (ECCs) and ECSCs. In contrast, miR-136, which was lowly expressed in endometrial cancer and ECSCs, had the opposite effect, and knockdown miR-136 inhibited the anticancer effects of down-regulated PVT1. PVT1 affected miR-136 specifically binding the 3’ UTR region of Sox2 by competitively “sponging” miR-136, thus positively saving Sox2. Sox2 promoted the malignant behavior and the stemness of ECCs and ECSCs, and overexpression Sox2 inhibited the anticancer effects of up-regulated miR-136. Sox2 can act as a transcription factor to positively regulate Up-frameshift protein 1 (UPF1) expression, thereby exerting a tumor-promoting effect on endometrial cancer. In nude mice, simultaneously downregulating PVT1 and upregulating miR-136 exerted the strongest antitumor effect. We demonstrate that the PVT1/miR-136/Sox2/UPF1 axis plays an important role in the progression and maintenance of endometrial cancer. The results suggest a novel target for endometrial cancer therapies.

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“…When GLUT3 is highly expressed in colorectal cancer (CRC) it is negatively linked to CRC patient outcome. GLUT3 expression protects CRC cells by energy stress in the tumour microenvironment to withstand nutrient scarcity and to exacerbate the malignancy of CRC cells [ 69 ].…”

Section: Rage Ligands In Crcmentioning

confidence: 99%

Cross-talks in colon cancer between RAGE/AGEs axis and inflammation/immunotherapy

et al. 2021

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The tumour microenvironment is the result of the activity of many types of cells in various metabolic states, whose metabolites are shared between cells. This cellular complexity results in an availability profile of nutrients and reactive metabolites such as advanced glycation end products (AGE). The tumour microenvironment is not favourable to immune cells due to hypoxia and for the existence of significant competition between various types of cells for a limited nutrient pool. However, it is now known that cancer cells can influence the host's immune reaction through the expression and secretion of numerous molecules. The microenvironment can therefore present itself in different patterns that contribute to shaping immune surveillance. Colorectal cancer (CRC) is one of the most important causes of death in cancer patients. Recently, immunotherapy has begun to give encouraging results in some groups of patients suffering from this neoplasm. The analysis of literature data shows that the RAGE (Receptor for advanced glycation end products) and its numerous ligands contribute to connect the energy metabolic pathway, which appears prevalently disconnected by mitochondrial running, with the immune reaction, conditioned by local microbiota and influencing tumour growth. Understanding how metabolism in cancer and immune cells shapes response and resistance to therapy, will provide novel potential strategies to increase both the number of tumour types treated by immunotherapy and the rate of immunotherapy response. The analysis of literature data shows that an immunotherapy approach based on the knowledge of RAGE and its ligands is not only possible, but also desirable in the treatment of CRC.

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UPF1 promotes chemoresistance to oxaliplatin through regulation of TOP2A activity and maintenance of stemness in colorectal cancer

Cited by 20 publications

References 56 publications

DNA Topoisomerase II-α Regulated by miR-22-5p Promotes Hepatocellular Carcinoma Invasion and Migration through the Hippo Pathway

DNA Topoisomerase II-α Regulated by miR-22-5p Promotes Hepatocellular Carcinoma Invasion and Migration through the Hippo Pathway

PVT1/miR-136/Sox2/UPF1 axis regulates the malignant phenotypes of endometrial cancer stem cells

Cross-talks in colon cancer between RAGE/AGEs axis and inflammation/immunotherapy

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