Knockdown of RFC4 inhibits the cell proliferation of nasopharyngeal carcinoma in vitro and in vivo

Guan, Shuzhen; Feng, Lin; Ji, Wei; Wang, Guizhen; Wu, Li

doi:10.1007/s11684-022-0938-x

Cited by 8 publications

(8 citation statements)

References 39 publications

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“…Flow cytometry, MTT and colony formation assays as well as transwell and wound healing assays also demonstrated that the cell cycle regulation, cell proliferation and migration affected by ACAT1 knockdown or overexpression can be reversed by SC79 or MK2206. RNA-seq heatmap analysis and qRT-PCR validation confirmed the downregulation of c-Myc downstream molecules in ACAT1 knockdown BLCA cells, linking these molecules to cell cycle regulation and proliferation in various malignancies, including glioblastoma [52,53], nasopharyngeal carcinoma [54], esophageal cancer [55], breast cancer [56,57], cervical cancer [58], lung cancer [59], liver cancer [60][61][62], bladder cancer [63], prostate cancer [64], acute myeloid leukemia [65] and diffuse large B-cell lymphoma [66]. In addition, reports on c-Myc-regulated downstream molecules involved in EMT, such as POLD2 [52], TMEM97 [56], DCTPP1 [64], MCM6 [61] and CBX3 [53], have been published.…”

Section: Discussionmentioning

confidence: 80%

ACAT1 promotes proliferation and metastasis of bladder cancer via AKT/GSK3β/c-Myc signaling pathway

Wang,

Shan

et al. 2024

J. Cancer

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Acetyl-CoA acetyltransferase 1 (ACAT1) plays a significant role in the regulation of gene expression and tumorigenesis. However, the biological role of ACAT1 in bladder cancer (BLCA) has yet to be elucidated. This research aimed to elucidate the bioinformatics features and biological functions of ACAT1 in BLCA. Here, we demonstrate that ACAT1 is elevated in BLCA tissues and is correlated with specific clinicopathological features and an unfavorable prognosis for survival in BLCA patients. ACAT1 was identified as an independent risk factor in BLCA. Phenotypically, both in vitro and in vivo , ACAT1 knockdown suppressed BLCA cell proliferation and migration, while ACAT1 overexpression had the opposite effect. Mechanistic assays revealed that ACAT1 enhances BLCA cell proliferation and metastasis through the AKT/GSK3β/c-Myc signaling pathway by modulating the cell cycle and EMT. Taken together, the results of our study reveal that ACAT1 is an oncogenic driver in BLCA that enhances tumor proliferation and metastasis, indicating its potential as a diagnostic and therapeutic target for this disease.

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Section: Discussionmentioning

confidence: 80%

ACAT1 promotes proliferation and metastasis of bladder cancer via AKT/GSK3β/c-Myc signaling pathway

Wang,

Shan

et al. 2024

J. Cancer

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“…It is worth noting that HOXA10 has been discovered as a downstream target of RFC4. Furthermore, HOXA10 overexpression has been shown to mitigate suppression of RFC4-induced cell proliferation, inhibition of colony formation, and cell cycle arrest [ 15 ]. In their study, Liu et al discovered that RFC4, a DNA replication factor, is amplified in over 40% of NSCLC tissues.…”

Section: Discussionmentioning

confidence: 99%

“…Through this investigation, we identified six proteins, MCM3, RFC2, PCNA, RFC5, KIF23, and TRAIP, that were consistently present in both the “RFC4-interacting” and “RFC4-correlated” protein groups. Given the established correlation of these proteins with the progression of multiple human cancers, as indicated in references [ 15 , 51 ], their interaction pathway with RFC4 emerged as a promising target for developing innovative antitumor treatments. This finding underscores the potential of targeting specific molecular interactions within cancer pathways as a therapeutic strategy.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, any perturbation in the functioning of RFC4 may play a role in cellular proliferation and tumor formation, and its aberrant expression has been recognized as a potentially significant prognostic indicator for a range of cancer types [ 15 , 16 , 17 ]. Nevertheless, the precise role of RFC4 in cancer initiation and advancement is still a subject of active investigation.…”

Section: Introductionmentioning

confidence: 99%

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Oncogenic Potential of Replication Factor C Subunit 4: Correlations with Tumor Progression and Assessment of Potential Inhibitors

Alaa Eldeen,

Mamdouh,

Abdulsahib

et al. 2024

Pharmaceuticals

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Replication Factor C Subunit 4 (RFC4), an oncogene implicated in many human cancers, has yet to be extensively studied in many cancer types to determine its expression patterns and tumor tissue function. Various bioinformatics tools were used to analyze RFC4 as a potential oncogene and therapeutic target across many cancers. We first examined RFC4 expression levels in several human tumor types to determine relationships with tumor grade, stage, metastasis, and patient survival. We also examined RFC4’s genetic changes, epigenetic methylation, and effect on tumor microenvironment (TME) immune cell infiltration. We also analyzed RFC4’s connections with immunological checkpoints to identify potential molecular pathways involved in carcinogenesis. Our findings show that RFC4 is upregulated in several tumor types and associated with poor prognoses in many human cancers. This study shows that RFC4 significantly affects the tumor immunological microenvironment, specifically immune cell populations. Finally, we screened for RFC4-inhibiting pharmacological compounds with anti-cancer potential. This study fully elucidates RFC4’s carcinogenic activities, emphasizing its potential as a prognostic biomarker and a target for anti-cancer therapy.

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“…The animal studies were performed according to protocols approved by the Animal Ethics Committee of Guangxi University (GXU-2022-161). A subcutaneous tumor bearing mice model was constructed as reported previously after 5–10 min of perfusion with isoflurane with rodent anesthesia machine [ 41 ]. Briefly, 5–6-week-old female BALB/C nude mice were purchased from Charles River (Beijing, China) and HepG2 cells with 5 × 10 6 /ml were subcutaneously injected into the right flank.…”

Section: Methodsmentioning

confidence: 99%

Sophoridine derivative 6j inhibits liver cancer cell proliferation via ATF3 mediated ferroptosis

Tian

Wang

et al. 2023

Cell Death Discov.

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Liver cancer is one of the most lethal malignancies with an annual death of over 830,000 cases. Although targeted therapeutic drugs have achieved certain clinical efficacy, only sorafenib and lenvatinib are currently marketed as first-line targeted drugs to treat patients with advanced liver cancer. Therefore, developing more drugs are urgently needed. Ferroptosis is an iron-dependent programmed cell death (PCD) distinct from known PCDs including apoptosis, necrosis, and autophagy. Targeting ferroptosis is recognized as a promising potential therapeutic modality for liver cancer. Activating transcription factor 3 (ATF3) is an important ferroptosis inducer and targeting ATF3 offers a potential means to cancer therapy. In the present study, we reported for the first time a sophoridine derivative 6j with promising anti-liver cancer effects in vitro and in vivo. Compound 6j could induce liver cancer cells ferroptosis by promoting the accumulation of intracellular Fe2+, reactive oxygen species (ROS), and MDA. Inhibition of ferroptosis by ferrostatin-1 alleviated 6j induced accumulation of Fe2+, ROS, and MDA and restored cell viability. Further study revealed that compound 6j upregulated the expression of ATF3 via ER stress and knockdown of ATF3 by RNA interference attenuated 6j induced ferroptosis and cell proliferation inhibition. This study would provide new insights for the design of ferroptosis inducers and the development of anti-liver cancer drugs.

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Knockdown of RFC4 inhibits the cell proliferation of nasopharyngeal carcinoma in vitro and in vivo

Cited by 8 publications

References 39 publications

ACAT1 promotes proliferation and metastasis of bladder cancer via AKT/GSK3β/c-Myc signaling pathway

ACAT1 promotes proliferation and metastasis of bladder cancer via AKT/GSK3β/c-Myc signaling pathway

Oncogenic Potential of Replication Factor C Subunit 4: Correlations with Tumor Progression and Assessment of Potential Inhibitors

Sophoridine derivative 6j inhibits liver cancer cell proliferation via ATF3 mediated ferroptosis

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