Terpenoids-enriched fraction of Celastrus orbiculatus sensitizes gemcitabine by disrupting Chk1/RAD51-mediated DNA damage response in pancreatic cancer

Zhao, Yang; Jiang, Zhuangzhuang; Ni, Tengyang; Jiang, Wei; Zhou, Kehui; Liu, Yuping; Liu, Yanqing; Li, Tao

doi:10.1007/s42764-021-00055-w

Cited by 5 publications

(2 citation statements)

References 37 publications

(46 reference statements)

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“…[ 51 ] Therefore, combining DDR inhibitors with DNA damaging agents represents a logical strategy. [ 52 , 53 ] Toward this notion, combination trials of chemotherapeutics with VX‐970, an inhibitor of the ATR protein responsible for inducing HR DNA repair following replication stress, showed promising responses in chemotherapy‐resistant cancers. [ 52 ] Tumors also show marked increases in glucose consumption in comparison to non‐proliferating normal tissues [ 1 , 5 , 54 ] and glucose metabolism is involved in DNA repair in a multifarious manner.…”

Section: Discussionmentioning

confidence: 99%

Vanguard is a Glucose Deprivation‐Responsive Long Non‐Coding RNA Essential for Chromatin Remodeling‐Reliant DNA Repair

et al. 2022

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Glucosemetabolism contributes to DNA damage response pathways by regulating chromatin remodeling, double-strand break (DSB) repair, and redox homeostasis, although the underlying mechanisms are not fully established. Here, a previously uncharacterized long non-coding RNA is revealed that is call Vanguard which acts to promote HMGB1-dependent DNA repair in association with changes in global chromatin accessibility. Vanguard expression is maintained in cancer cells by SP1-dependent transcription according to glucose availability and cellular adenosine triphosphate (ATP) levels. Vanguard promotes complex formation between HMGB1 and HDAC1, with the resulting deacetylation of HMGB1 serving to maintain its nuclear localization and DSB repair function. However, Vanguard downregulation under glucose limiting conditions promotes HMGB1 translocation from the nucleus, increasing DNA damage, and compromising cancer cell growth and viability. Moreover, Vanguard silencing increases the effectiveness of poly (ADP-ribose) polymerase inhibitors against breast cancer cells with wild-type breast cancer gene-1 status, suggesting Vanguard as a potential therapeutic target.

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Section: Discussionmentioning

confidence: 99%

Vanguard is a Glucose Deprivation‐Responsive Long Non‐Coding RNA Essential for Chromatin Remodeling‐Reliant DNA Repair

et al. 2022

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“…Recently, we found that the loss of nhr-14 gene in c. elegans resulted in the dysregulation of DNA damage-induced response [14], which usually leads to cancer development [15][16][17][18]. Thus, we examined HNF4α expression levels in different cancers and matched paired normal tissues.…”

Section: Hnf4 α Promotes Colorectal Carcinogenesismentioning

confidence: 99%

HNF4α is a target of the Wnt/β-catenin pathway and regulates colorectal carcinogenesis

Sang,

Bai,

et al. 2024

Preprint

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Hepatocyte nuclear factor 4alpha (HNFalpha) is a transcription factor involved in liver function. Dysregulation of HNF4alpha leads to hepatocarcinogenesis. However, the role and mechanism of HNF4alpha; in colorectal cancer is still unknown. Here we demonstrate that HNF4alpha is upregulated in colorectal cancers. and HNF4alpha upregulation promotes colorectal tumorigenesis. Notably, expression levels of HNF4alpha are positively correlated with the Wnt/beta-catenin signaling pathway in colorectal cancer patients. Further, we showed that HNF4alpha is transcriptionally activated by Wnt/beta-catenin/TCF3 and is at least partially responsible for the oncognesis activity of the Wnt signaling in colorectal cancer. Our findings indicate that HNF4alpha is a direct target of that Wnt/beta-catenin pathway and could play an important role in colorectal carcinogenesis.

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Betulinic acid, a major therapeutic triterpene of Celastrus orbiculatus Thunb., acts as a chemosensitizer of gemcitabine by promoting Chk1 degradation

Zhou

Zhao

et al. 2023

Journal of Ethnopharmacology

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Terpenoids-enriched fraction of Celastrus orbiculatus sensitizes gemcitabine by disrupting Chk1/RAD51-mediated DNA damage response in pancreatic cancer

Cited by 5 publications

References 37 publications

Vanguard is a Glucose Deprivation‐Responsive Long Non‐Coding RNA Essential for Chromatin Remodeling‐Reliant DNA Repair

Vanguard is a Glucose Deprivation‐Responsive Long Non‐Coding RNA Essential for Chromatin Remodeling‐Reliant DNA Repair

HNF4α is a target of the Wnt/β-catenin pathway and regulates colorectal carcinogenesis

Betulinic acid, a major therapeutic triterpene of Celastrus orbiculatus Thunb., acts as a chemosensitizer of gemcitabine by promoting Chk1 degradation

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