CRISPR/Cas9 screens unravel miR-3689a-3p regulating sorafenib resistance in hepatocellular carcinoma via suppressing CCS/SOD1-dependent mitochondrial oxidative stress

Lu, Yuanjun; Chan, Yau-Tuen; Wu, Junyu; Feng, Zixin; Yuan, Hongchao; Li, Qiucheng; Xing, Tingyuan; Xu, Lin; Zhang, Cheng; Tan, Hor-Yue; Lee, Terence Kin-Wah; Feng, Yibin; Wang, Ning

doi:10.1016/j.drup.2023.101015

Cited by 16 publications

(2 citation statements)

References 53 publications

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“…Hepatocellular carcinoma is a primary cause of cirrhosis death with poor prognosis, and its mortalities approximated incidence rates worldwide [ 71 ]. The metastasis is a hallmark of cancer that account for the largest number of cancer-related death, the continuous advancement of cancer biology studies and the appearance of new paradigms in metastasis study have revealed several molecular underpinnings of this dissemination process [ 72 ], such as gene mutations, soluble signals, cell-cell interactions, microbiome, the adhesive signals from extracellular matrix components (EMC), EMC mechanical pressures and epigenetic factors.…”

Section: Discussionmentioning

confidence: 99%

Exploring the metastasis-related biomarker and carcinogenic mechanism in liver cancer based on single cell technology

Zheng,

Lu,

et al. 2024

Heliyon

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Section: Discussionmentioning

confidence: 99%

Exploring the metastasis-related biomarker and carcinogenic mechanism in liver cancer based on single cell technology

Zheng,

Lu,

et al. 2024

Heliyon

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“…Orthotopic mouse models showed that miR-3689a-3p downregulation decreased sorafenib efficacy. Since lower miR-3689a-3p levels were detected in tumor specimens from HCC patient cohorts, the study paves the way towards a combined miRNA mimic and sorafenib strategy to boost sorafenib's anticancer efficacy [54]. Notably, this high-throughput screening procedure is particularly suitable for the discovery of driver genes and therapeutic targets that modulate drug efficacy.…”

Section: Crispr/cas9 High-throughput Screening Identifies Mirnas With...mentioning

confidence: 97%

Noncoding RNAs in Hepatocellular Carcinoma: Potential Applications in Combined Therapeutic Strategies and Promising Candidates of Treatment Response

Vianello,

Monti,

Leoni

et al. 2024

Cancers

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The incidence of hepatocellular carcinoma (HCC) is increasing, and 40% of patients are diagnosed at advanced stages. Over the past 5 years, the number of clinically available treatments has dramatically increased for HCC, making patient management particularly complex. Immune checkpoint inhibitors (ICIs) have improved the overall survival of patients, showing a durable treatment benefit over time and a different response pattern with respect to tyrosine kinase inhibitors (TKIs). Although there is improved survival in responder cases, a sizeable group of patients are primary progressors or are ineligible for immunotherapy. Indeed, patients with nonviral etiologies, such as nonalcoholic steatohepatitis (NASH), and alterations in specific driver genes might be less responsive to immunotherapy. Therefore, improving the comprehension of mechanisms of drug resistance and identifying biomarkers that are informative of the best treatment approach are required actions to improve patient survival. Abundant evidence indicates that noncoding RNAs (ncRNAs) are pivotal players in cancer. Molecular mechanisms through which ncRNAs exert their effects in cancer progression and drug resistance have been widely investigated. Nevertheless, there are no studies summarizing the synergistic effect between ncRNA-based strategies and TKIs or ICIs in the preclinical setting. This review aims to provide up-to-date information regarding the possible use of ncRNAs as therapeutic targets in association with molecular-targeted agents and immunotherapies and as predictive tools for the selection of optimized treatment options in advanced HCCs.

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Loss of Carbamoyl Phosphate Synthetase 1 Potentiates Hepatocellular Carcinoma Metastasis by Reducing Aspartate Level

Chen,

Tang,

et al. 2024

Advanced Science

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Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide. Numerous studies have shown that metabolic reprogramming is crucial for the development of HCC. Carbamoyl phosphate synthase 1 (CPS1), a rate‐limiting enzyme in urea cycle, is an abundant protein in normal hepatocytes, however, lacking systemic research in HCC. It is found that CPS1 is low‐expressed in HCC tissues and circulating tumor cells, negatively correlated with HCC stage and prognosis. Further study reveals that CPS1 is a double‐edged sword. On the one hand, it inhibits the activity of phosphatidylcholine‐specific phospholipase C to block the biosynthesis of diacylglycerol (DAG), leading to the downregulation of the DAG/protein kinase C pathway to inhibit invasion and metastasis of cancer cells. On the other hand, CPS1 promotes cell proliferation by increasing intracellular S‐adenosylmethionin to enhance the m6A modification of solute carrier family 1 member 3 mRNA, a key transporter for aspartate intake. Finally, CPS1 overexpressing adeno‐associated virus can dampen HCC progression. Collectively, this results uncovered that CPS1 is a switch between HCC proliferation and metastasis by increasing intracellular aspartate level.

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CRISPR/Cas9 screens unravel miR-3689a-3p regulating sorafenib resistance in hepatocellular carcinoma via suppressing CCS/SOD1-dependent mitochondrial oxidative stress

Cited by 16 publications

References 53 publications

Exploring the metastasis-related biomarker and carcinogenic mechanism in liver cancer based on single cell technology

Exploring the metastasis-related biomarker and carcinogenic mechanism in liver cancer based on single cell technology

Noncoding RNAs in Hepatocellular Carcinoma: Potential Applications in Combined Therapeutic Strategies and Promising Candidates of Treatment Response

Loss of Carbamoyl Phosphate Synthetase 1 Potentiates Hepatocellular Carcinoma Metastasis by Reducing Aspartate Level

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