Bcl-xL DNAzymes promote radiosensitivity and chemosensitivity in colorectal cancer cells via enhancing apoptosis

Yu, Zhen; Guo, Jianbin; Meng, Tao; Liu, Ge; Liu, Lin; Wang, Haijiang; Yang, Xinggang

doi:10.1186/s40360-022-00553-x

Cited by 4 publications

(4 citation statements)

References 48 publications

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“…Vitamin D has been found to enhance cisplatin chemotherapy and is suggested to be supplied during chemotherapy [ 35 ]. Through enhancing apoptosis, multiple molecules (e.g., Bcl-xL DNAzymes) promote radiosensitivity and chemosensitivity in cancer cells [ 36 ]. Recently, Jaidee et al showed that the inhibition of fibroblast growth factor receptor 2 enhances chemosensitivity to gemcitabine in cholangiocarcinoma [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Role of PPARG in Chemosensitivity-Regulating Network for Hypopharyngeal Squamous Cell Carcinoma

Kong,

Han,

Chen

et al. 2023

PPAR Research

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PPARG has been reported to promote chemosensitivity in hypopharyngeal squamous cell carcinoma (HSCC). However, few studies tested its significance in the texture of a complex molecular network regulating chemosensitivity in HSCC. Here, we first employed RNA expression data analysis and literature data mining to uncover candidate genes related to HSCC chemosensitivity. Then, we constructed the molecular network regulating chemosensitivity in HSCC. After that, we employed degree centrality (DC) and weighted centrality (WC) to test the significance of PPARG within the regulating network. Pathway enrichment was done to study the cofunctions of PPARG and the rest of the genes within the network. The findings of our study contribute to the construction of a comprehensive network that regulates HSCC chemosensitivity, consisting of 57 genes, including PPARG. Notably, within this network, PPARG demonstrates a ranking of #5 and #13 based on DC and WC, respectively. Moreover, PPARG is connected to 29 out of the 57 genes and plays roles in multiple functional groups. These top related genes include AKT1, TP53, PTEN, MAPK1, NOTCH1, BECN1, PTGS2, SPP1, and RAC1. PPARG gets enriched in several key functional groups that have been implicated in the regulation of chemosensitivity, including those associated with the response to nutrients, vitamins, and peptides, the cellular response to chemical stress, and the regulation of hormone secretion and growth. Our results emphasize the involvement of PPARG and its interconnectedness with other genes in the regulation of HSCC chemosensitivity.

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Section: Discussionmentioning

confidence: 99%

Role of PPARG in Chemosensitivity-Regulating Network for Hypopharyngeal Squamous Cell Carcinoma

Kong,

Han,

Chen

et al. 2023

PPAR Research

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“…Therefore, these Bcl-xL targeting enzymes (DT882, DT883, and DT884) suppressed the expression of Bcl-xL and made RC cells more sensitive to 5-FU and radiotherapy. 82 , 83 …”

Section: Mechanisms Of Sensitizing Tumors To Radiationmentioning

confidence: 99%

Understanding the molecular mechanism responsible for developing therapeutic radiation-induced radioresistance of rectal cancer and improving the clinical outcomes of radiotherapy - A review

Jain,

Nagainallur Ravichandran,

Murali Kumar

et al. 2024

Cancer Biology & Therapy

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Rectal cancer accounts for the second highest cancer-related mortality, which is predominant in Western civilizations. The treatment for rectal cancers includes surgery, radiotherapy, chemotherapy, and immunotherapy. Radiotherapy, specifically external beam radiation therapy, is the most common way to treat rectal cancer because radiation not only limits cancer progression but also significantly reduces the risk of local recurrence. However, therapeutic radiation-induced radioresistance to rectal cancer cells and toxicity to normal tissues are major drawbacks. Therefore, understanding the mechanistic basis of developing radioresistance during and after radiation therapy would provide crucial insight to improve clinical outcomes of radiation therapy for rectal cancer patients. Studies by various groups have shown that radiotherapy-mediated changes in the tumor microenvironment play a crucial role in developing radioresistance. Therapeutic radiation-induced hypoxia and functional alterations in the stromal cells, specifically tumor-associated macrophage (TAM) and cancer-associated fibroblasts (CAF), play a crucial role in developing radioresistance. In addition, signaling pathways, such as – the PI3K/AKT pathway, Wnt/β-catenin signaling, and the hippo pathway, modulate the radiation responsiveness of cancer cells. Different radiosensitizers, such as small molecules, microRNA, nanomaterials, and natural and chemical sensitizers, are being used to increase the effectiveness of radiotherapy. This review highlights the mechanism responsible for developing radioresistance of rectal cancer following radiotherapy and potential strategies to enhance the effectiveness of radiotherapy for better management of rectal cancer.

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“…Yu et al used DNAzymes to downregulate Bcl-xL mRNA expression to enhance the radiosensitivity and chemosensitivity of the chemotherapeutic drug Fluorouracil (5-FU). [183] Prodrug-mediated tumor in situ activation combined with DNAzyme-mediated gene therapy is a new synergistic therapeutic strategy. A biMOF-encapsulated DNAzyme system was developed to activate anticancer drugs in cancer cells and deplete EGR-1 mRNA mediated by DNAzymes (Figure 11F).…”

Section: Dnazymes In Chemotherapymentioning

confidence: 99%

“…used DNAzymes to downregulate Bcl‐xL mRNA expression to enhance the radiosensitivity and chemosensitivity of the chemotherapeutic drug Fluorouracil (5‐FU). [ 183 ]…”

Section: Recent Synergistic Strategies To Improve Dnazyme Therapeutic...mentioning

confidence: 99%

Therapeutic DNAzymes: From Structure Design to Clinical Applications

et al. 2023

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Therapeutic DNAzymes have unceasingly intrigued the scientific community owing to their prosperous gene regulation capability. The efficacy of DNAzymes against many types of diseases has been extensively studied for over two decades. However, the high expectations for DNAzymes are still not translated to the clinic because of their low effectiveness in vivo. Over the last five years, several aspects have been considered to optimize DNAzyme‐integrated therapeutics, including structural stability, mechanism exploration, cell internalization rate, cofactor activation, and off‐target effects. Hence, this review first discusses the early monotherapy and structural design of DNAzymes. Subsequently, the latest modes of action are reviewed, followed by an elaboration on structural stabilization strategies considering the catalytic core and substrate‐binding arms. DNAzyme‐based synergistic therapy is then examined, highlighting responsive carrier construction, synergistic effects, the latest discovered advanced functions, and off‐target concerns. Beyond this, key clinical advances in DNAzyme‐based therapy are elucidated by showcasing clinical progress. Finally, future trends and development challenges for DNAzyme‐powered therapeutics in the coming years are discussed in detail.

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Bcl-xL DNAzymes promote radiosensitivity and chemosensitivity in colorectal cancer cells via enhancing apoptosis

Cited by 4 publications

References 48 publications

Role of PPARG in Chemosensitivity-Regulating Network for Hypopharyngeal Squamous Cell Carcinoma

Role of PPARG in Chemosensitivity-Regulating Network for Hypopharyngeal Squamous Cell Carcinoma

Understanding the molecular mechanism responsible for developing therapeutic radiation-induced radioresistance of rectal cancer and improving the clinical outcomes of radiotherapy - A review

Therapeutic DNAzymes: From Structure Design to Clinical Applications

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