Silencing GS Homeobox 2 Alleviates Gemcitabine Resistance in Pancreatic Cancer Cells by Activating SHH/GLI1 Signaling Pathway

Zhuang, Lu; Yao, Yao; Peng, Lisi; Cui, Fang; Zhang, Yang; Sun, Lixia; Yu, Qihong; Lin, Kun

doi:10.1007/s10620-021-07262-1

Cited by 4 publications

(2 citation statements)

References 35 publications

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“…The effects of the Hh signaling pathway are achieved through the transcription of downstream target genes upregulated by the nuclear transcription factor Gli1. The effects of Gli1 in promoting pancreatic cancer proliferation and invasion were verified in this study, and our results were consistent with those reported in the literature [ 23 , 24 ].…”

Section: Discussionsupporting

confidence: 93%

Hedgehog-Gli1-derived exosomal circ-0011536 mediates peripheral neural remodeling in pancreatic cancer by modulating the miR-451a/VGF axis

Dai,

Wu,

et al. 2023

J Exp Clin Cancer Res

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Background Hedgehog-Gli1 signaling induces development of two common neurological features seen in pancreatic ductal adenocarcinoma (PDAC): peripheral neural invasion (PNI) and peripheral neural remodeling (PNR). However, the underlying molecular mechanisms in cancer cells and nerves within Gli1-derived PNR have not previously been comprehensively analyzed. Methods In this study, RNA sequencing was used to screen meaningful circRNAs in PNR. An in vitro model of PNR was subsequently constructed through a co-culture system comprising PDAC cells and murine dorsal root ganglia (DRG) (as the neuronal element), and the relevant mechanisms were explored using a series of molecular biology experiments. A subcutaneous nude mouse tumorigenesis model was established to further verify the occurrence of PNR that was detected in human PDAC samples. Results We first confirmed the molecular mechanisms of PNR development through crosstalk between exosomal circ-0011536 and DRG. In Gli1-overpressed PDAC, circ-0011536 is mainly secreted by exosomes. After being ingested by DRG, it can promote the activity of DRG by degrading miR-451a and upregulating the expression of VGF. Overexpression of Gli1 can accelerate the proliferation of subcutaneous tumors in mice and is closely related to the density of nerve plexuses, while downregulating circ-RNA inhibits tumor proliferation and reduces the density of nerve plexuses. In addition, TMA results confirmed that Gli1 overexpression significantly increased the expression of VGF and was closely associated with increased nerve plexus density. Conclusion Hedgehog-Gli1-induced exosomal circ-0011536 promoted PNR via the miR-451a/VGF axis, thereby establishing that it may contribute to PDAC-associated nerve changes with activated Hedgehog signaling.

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Section: Discussionsupporting

confidence: 93%

Hedgehog-Gli1-derived exosomal circ-0011536 mediates peripheral neural remodeling in pancreatic cancer by modulating the miR-451a/VGF axis

Dai,

Wu,

et al. 2023

J Exp Clin Cancer Res

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“…IHC was used to measure the levels of CASP5, GZMB, GBP1, IL1B, and IRF1 in colonic tissues as previously described [27]. The primary antibodies applied were CASP 5 (1 : 400, Boster, A05259-4), GZMB (1 : 3000, abcam, ab255598), GBP1 (1 : 300; Proteintech, 15303-1-AP), IL1B (1 : 500; abcam, ab283818), and IRF-1 (1 : 400, Cell Signaling Technology, 8478).…”

Section: Mouse Tissue Processing and Immunohistochemistry (Ihc)mentioning

confidence: 99%

Pyroptosis-Related Signature Predicts the Progression of Ulcerative Colitis and Colitis-Associated Colorectal Cancer as well as the Anti-TNF Therapeutic Response

Ning

Lin

Fang

et al. 2023

Journal of Immunology Research

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Ulcerative colitis (UC) is a complex intestinal inflammation with an increasing risk of colitis-associated colorectal cancer (CAC). However, the pathogenesis is still unclear between active UC and inactive UC. Recently, it has been reported that pyroptosis-related genes (PRGs) are closely associated with inflammatory disease activity. Nevertheless, the specific roles of PRGs in the progression and treatment of UC and CAC remain unclear. In this study, we identified 30 differentially expressed PRGs based on the immune landscape of active and inactive UC samples. Meanwhile, weighted gene coexpression network analysis was applied to explore important genes associated with active UC. By intersecting with the differentially expressed PRGs, CASP5, GBP1, GZMB, IL1B, and IRF1 were selected as key PRGs to construct a pyroptosis-related signature (PR-signature). Then, logistic regression analysis was performed to validate the PR-signature and establish a pyroptosis-related score (PR-Score). We demonstrated that PR-Score had a powerful ability to distinguish active UC from inactive UC in multiple datasets. Besides, PR-Score was positively correlated with immune cell infiltration and inflammatory microenvironment in UC. Lower PR-Score was associated with a better response to anti-TNF therapy for patients with UC. Additionally, high-PR-Score was found to suppress CAC and improve the survival outcomes of patients with colorectal cancer. Finally, the levels of the PR-signature genes were validated both in vitro and in vivo. These findings can improve our understanding of PRGs in UC and provide new markers for predicting the occurrence of active UC or CAC and the treatment of UC.

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Nrf2‐mediated adenylosuccinate lyase promotes resistance to gemcitabine in pancreatic ductal adenocarcinoma cells through ferroptosis escape

Hsu,

Wang,

Chen

et al. 2024

Journal Cellular Physiology

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Pancreatic cancer has one of the highest fatality rates and the poorest prognosis among all cancer types worldwide. Gemcitabine is a commonly used first‐line therapeutic drug for pancreatic cancer; however, the rapid development of resistance to gemcitabine treatment has been observed in numerous patients with pancreatic cancer, and this phenomenon limits the survival benefit of gemcitabine. Adenylosuccinate lyase (ADSL) is a crucial enzyme that serves dual functions in de novo purine biosynthesis, and it has been demonstrated to be associated with clinical aggressiveness, prognosis, and worse patient survival for various cancer types. In the present study, we observed significantly lower ADSL levels in gemcitabine‐resistant cells (PANC‐1/GemR) than in parental PANC‐1 cells, and the knockdown of ADSL significantly increased the gemcitabine resistance of parental PANC‐1 cells. We further demonstrated that ADSL repressed the expression of CARD‐recruited membrane‐associated protein 3 (Carma3), which led to increased gemcitabine resistance, and that nuclear factor erythroid 2‐related factor 2 (Nrf2) regulated ADSL expression in parental PANC‐1 cells. These results indicate that ADSL is a candidate therapeutic target for pancreatic cancer involving gemcitabine resistance and suggest that the Nrf2/ADSL/Carma3 pathway has therapeutic value for pancreatic cancer with acquired resistance to gemcitabine.

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Silencing GS Homeobox 2 Alleviates Gemcitabine Resistance in Pancreatic Cancer Cells by Activating SHH/GLI1 Signaling Pathway

Cited by 4 publications

References 35 publications

Hedgehog-Gli1-derived exosomal circ-0011536 mediates peripheral neural remodeling in pancreatic cancer by modulating the miR-451a/VGF axis

Hedgehog-Gli1-derived exosomal circ-0011536 mediates peripheral neural remodeling in pancreatic cancer by modulating the miR-451a/VGF axis

Pyroptosis-Related Signature Predicts the Progression of Ulcerative Colitis and Colitis-Associated Colorectal Cancer as well as the Anti-TNF Therapeutic Response

Nrf2‐mediated adenylosuccinate lyase promotes resistance to gemcitabine in pancreatic ductal adenocarcinoma cells through ferroptosis escape

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