Single-PanIN-seq unveils that ARID1A deficiency promotes pancreatic tumorigenesis by attenuating KRAS-induced senescence

Liu, Shou; Cao, Wenjian; Niu, Yichi; Luo, Jiayi; Zhao, Yanhua; Hu, Zheng; Zong, Chenghang

doi:10.7554/elife.64204

Cited by 8 publications

(7 citation statements)

References 45 publications

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“…The induction of oncogene-induced senescence was performed as described in previous publicaiton 49 . Briefly, wild-type HPNE cells with inducible KRAS G12D (iKRAS-HPNE) were cultured with doxycycline (6 μg/mL) to activate the expression of KRAS G12D .…”

Section: Methods Cell Culturesmentioning

confidence: 99%

Single-cell Total-RNA Profiling Unveils Regulatory Hubs of Transcription Factors

Niu,

Luo,

Zong

2023

Preprint

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Recent development of RNA velocity uses master equations to establish the kinetics of the life cycle of RNAs from nascent RNA to mature RNA to degradation. To feed this kinetic analysis, simultaneous measurement of nascent RNA and mature RNA in single cells is greatly desired. However, the majority of single-cell RNA-seq chemistry only captures mature RNA species to measure gene expressions. Here, we develop a one-step total-RNA chemistry-based scRNA-seq method: snapTotal-seq. We benchmarked this method with multiple single-cell RNA-seq assays in their performance in kinetic analysis of cell cycle by RNA velocity. Next, with LASSO regression between transcription factors, we identified the critical regulatory hubs mediating the cell cycle dynamics. We also applied snapTotal-seq to profile the oncogene-induced senescence and identified the key regulatory hubs governing the entry of senescence. Furthermore, from the comparative analysis of nascent RNA and mature RNA, we identified a significant portion of genes whose expression changes occurred in mature RNA but not to the same degree in nascent RNA, indicating these gene expression changes are mainly controlled by post-transcriptional regulation. Overall, we demonstrate that snapTotal-seq can provide enriched information about gene regulation, especially during the transition between cell states.

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Section: Methods Cell Culturesmentioning

confidence: 99%

Single-cell Total-RNA Profiling Unveils Regulatory Hubs of Transcription Factors

Niu,

Luo,

Zong

2023

Preprint

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“…ALDH1A3 promotes pancreatic cancer metastasis through its metabolic effects on glucose metabolism, and PPARγ and its downstream PI3K/AKT/mTOR signaling pathway may be involved in this process ( 215 ). Furthermore, the expression of ALDH1 in these solid tumors is also affected by Notch1 signaling ( 216 ), ILK signaling ( 217 ), Hippo signaling ( 218 ), miR-761 ( 219 ), ARID1A deficiency ( 220 ), IL17 ( 221 ), etc.…”

Section: Aldh1 and Various Solid Tumorsmentioning

confidence: 99%

“…ALDH1 can maintain stem cell characteristics and lead to drug resistance, which is the key to tumor recurrence and is difficult to cure. Preclinical studies have shown that ALDH1 plays an essential role in the occurrence, invasion, and metastasis of different cancers through various pathways ( 20 ) ( 220 ) ( 22 ) ( 23 ). In recent years, many scholars have studied ALDH1 inhibitors and targeting ALDH1, but there is no clinical evidence on the efficacy and safety of their inhibition in solid tumors.…”

Section: Prospectivementioning

confidence: 99%

ALDH1: A potential therapeutic target for cancer stem cells in solid tumors

Wei

Chen

et al. 2022

Front. Oncol.

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Solid tumors can be divided into benign solid tumors and solid malignant tumors in the academic community, among which malignant solid tumors are called cancers. Cancer is the second leading cause of death in the world, and the global incidence of cancer is increasing yearly New cancer patients in China are always the first. After the concept of stem cells was introduced in the tumor community, the CSC markers represented by ALDH1 have been widely studied due to their strong CSC cell characteristics and potential to be the driving force of tumor metastasis. In the research results in the past five years, it has been found that ALDH1 is highly expressed in various solid cancers such as breast cancer, lung cancer, colorectal cancer, liver cancer, gastric cancer, cervical cancer, esophageal cancer, ovarian cancer, head,and neck cancer. ALDH1 can activate and transform various pathways (such as the USP28/MYC signaling pathway, ALDH1A1/HIF-1α/VEGF axis, wnt/β-catenin signaling pathway), as well as change the intracellular pH value to promote formation and maintenance, resulting in drug resistance in tumors. By targeting and inhibiting ALDH1 in tumor stem cells, it can enhance the sensitivity of drugs and inhibit the proliferation, differentiation, and metastasis of solid tumor stem cells to some extent. This review discusses the relationship and pathway of ALDH1 with various solid tumors. It proposes that ALDH1 may serve as a diagnosis and therapeutic target for CSC, providing new insights and new strategies for reliable tumor treatment.

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“…The depletion of PHF10 induced cell cycle arrest and a senescence-like phenotypes [ 133 ]. Recently, ARID1A, a paralog of ARID1B, whose deficiency is implicated in the promotion of cancer progression, was identified as being able to induce senescence and the progression of pancreatic intraepithelial neoplasia (PanIN) [ 134 ]. Moreover, the loss of function of the SWI/SNF complex via the deletion of specific subunits such as BRD7, SNF5, or PBR1 resulted in a senescence bypass and was relevant to tumorigenesis [ 37 , 135 , 136 ].…”

Section: Effects Of Chromatin Remodeler Deregulation On Cancer Progre...mentioning

confidence: 99%

Targeting Chromatin-Remodeling Factors in Cancer Cells: Promising Molecules in Cancer Therapy

Zhang

2022

IJMS

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ATP-dependent chromatin-remodeling complexes can reorganize and remodel chromatin and thereby act as important regulator in various cellular processes. Based on considerable studies over the past two decades, it has been confirmed that the abnormal function of chromatin remodeling plays a pivotal role in genome reprogramming for oncogenesis in cancer development and/or resistance to cancer therapy. Recently, exciting progress has been made in the identification of genetic alteration in the genes encoding the chromatin-remodeling complexes associated with tumorigenesis, as well as in our understanding of chromatin-remodeling mechanisms in cancer biology. Here, we present preclinical evidence explaining the signaling mechanisms involving the chromatin-remodeling misregulation-induced cancer cellular processes, including DNA damage signaling, metastasis, angiogenesis, immune signaling, etc. However, even though the cumulative evidence in this field provides promising emerging molecules for therapeutic explorations in cancer, more research is needed to assess the clinical roles of these genetic cancer targets.

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Single-PanIN-seq unveils that ARID1A deficiency promotes pancreatic tumorigenesis by attenuating KRAS-induced senescence

Cited by 8 publications

References 45 publications

Single-cell Total-RNA Profiling Unveils Regulatory Hubs of Transcription Factors

Single-cell Total-RNA Profiling Unveils Regulatory Hubs of Transcription Factors

ALDH1: A potential therapeutic target for cancer stem cells in solid tumors

Targeting Chromatin-Remodeling Factors in Cancer Cells: Promising Molecules in Cancer Therapy

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