HNRNPC regulates RhoA to induce DNA damage repair and cancer‐associated fibroblast activation causing radiation resistance in pancreatic cancer

Xia, Ning; Yang, Nannan; Shan, Qungang; Wang, Ziyin; Liu, Xiaoyu; Chen, Yingjie; Lu, Junxi; Huang, Wei; Wang, Zhongmin

doi:10.1111/jcmm.17254

Cited by 13 publications

(11 citation statements)

References 48 publications

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“…A critical gene for DNA double-strand break repair, Brca1 (BRCA1 DNA Repair Associated) [ 66 ], had a 2.71-fold decrease in expression by the end of lactate adaptation. The gene with the greatest net downregulation, Hnrnpc (Heterogeneous Nuclear Ribomucleoprotein C), is a regulator of pre-mRNA processing and has been observed to be overexpressed in some cancers; however, a reduced expression of Hnrnpc has been shown to limit tumor proliferation [ 67 , 68 ]. Genes with a net differential expression change are shown in Table 3 .…”

Section: Resultsmentioning

confidence: 99%

Dynamics of Amino Acid Metabolism, Gene Expression, and Circulomics in a Recombinant Chinese Hamster Ovary Cell Line Adapted to Moderate and High Levels of Extracellular Lactate

Chitwood

et al. 2023

Genes

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The accumulation of metabolic wastes in cell cultures can diminish product quality, reduce productivity, and trigger apoptosis. The limitation or removal of unintended waste products from Chinese hamster ovary (CHO) cell cultures has been attempted through multiple process and genetic engineering avenues with varied levels of success. One study demonstrated a simple method to reduce lactate and ammonia production in CHO cells with adaptation to extracellular lactate; however, the mechanism behind adaptation was not certain. To address this profound gap, this study characterizes the phenotype of a recombinant CHO K-1 cell line that was gradually adapted to moderate and high levels of extracellular lactate and examines the genomic content and role of extrachromosomal circular DNA (eccDNA) and gene expression on the adaptation process. More than 500 genes were observed on eccDNAs. Notably, more than 1000 genes were observed to be differentially expressed at different levels of lactate adaptation, while only 137 genes were found to be differentially expressed between unadapted cells and cells adapted to grow in high levels of lactate; this suggests stochastic switching as a potential stress adaptation mechanism in CHO cells. Further, these data suggest alanine biosynthesis as a potential stress-mitigation mechanism for excess lactate in CHO cells.

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Section: Resultsmentioning

confidence: 99%

Dynamics of Amino Acid Metabolism, Gene Expression, and Circulomics in a Recombinant Chinese Hamster Ovary Cell Line Adapted to Moderate and High Levels of Extracellular Lactate

Chitwood

et al. 2023

Genes

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“…Dysregulation of HNRNPC has been observed in lung cancer, breast cancer, and oral squamous cell carcinoma patients ( 34–36 ). This gene has been shown to regulate tumor cell proliferation and promote radiation resistance in pancreatic cancer ( 37 ) and mediate mRNA stabilization to alter energy metabolism, facilitating metastasis and invasion of oral cancer cells ( 38 ). Collectively, these findings suggested that the top genes revealed by MitoTracer analysis may play a role in primary BRAF-inhibitor resistance and represent potential targets for reversing resistance.…”

Section: Resultsmentioning

confidence: 99%

MitoTracer facilitates the identification of informative mitochondrial mutations for precise lineage reconstruction

Yu,

Hu,

Tan

et al. 2023

Preprint

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Mitochondrial (MT) mutations serve as natural genetic markers for inferring clonal relationships using single cell sequencing data. However, the fundamental challenge of MT mutation-based lineage tracing is automated identification of informative MT mutations. Here, we introduced an open-source computational algorithm called “MitoTracer”, which accurately identified clonally informative MT mutations and inferred evolutionary lineage from scRNA-seq or scATAC-seq samples. We benchmarked MitoTracer using the ground-truth experimental lineage sequencing data and demonstrated its superior performance over the existing methods measured by high sensitivity and specificity. MitoTracer is compatible with multiple single cell sequencing platforms. Its application to a cancer evolution dataset revealed the genes related to primary BRAF-inhibitor resistance from scRNA-seq data of BRAF-mutated cancer cells. Overall, our work provided a valuable tool for capturing real informative MT mutations and tracing the lineages among cells.TeaserMitoTracer enables automatically and accurately discover informative mitochondrial mutations for lineage tracing.

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“…Similarly, A549 cells had weakened migration in response to the treatment with the Rho inhibitor CT04 [ 19 ]. Moreover, RhoA inhibition weakened the activity of cancer-related fibroblasts and overcame radiation resistance in pancreatic cancer [ 27 ]. Further studies are also essential to verify whether the interplay between CX3CL1/CX3CR1 and the RhoA signaling was also involved in the resistance to other chemotherapeutic agents and other types of cancers.…”

Section: Discussionmentioning

confidence: 99%

CX3CL1 and its receptor CX3CR1 interact with RhoA signaling to induce paclitaxel resistance in gastric cancer

Liu,

Yu,

et al. 2024

Heliyon

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HNRNPC regulates RhoA to induce DNA damage repair and cancer‐associated fibroblast activation causing radiation resistance in pancreatic cancer

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 13 publications

References 48 publications

Dynamics of Amino Acid Metabolism, Gene Expression, and Circulomics in a Recombinant Chinese Hamster Ovary Cell Line Adapted to Moderate and High Levels of Extracellular Lactate

Dynamics of Amino Acid Metabolism, Gene Expression, and Circulomics in a Recombinant Chinese Hamster Ovary Cell Line Adapted to Moderate and High Levels of Extracellular Lactate

MitoTracer facilitates the identification of informative mitochondrial mutations for precise lineage reconstruction

CX3CL1 and its receptor CX3CR1 interact with RhoA signaling to induce paclitaxel resistance in gastric cancer

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