Down‐regulation of RCC1 sensitizes immunotherapy by up‐regulating PD‐L1 via p27<sup>kip1</sup>/CDK4 axis in non‐small cell lung cancer

Zeng, Xiaozhu; Zhong, Ming; Yang, Yumeng; Wang, Zhi; Zhu, Yubing

doi:10.1111/jcmm.16383

Cited by 16 publications

(18 citation statements)

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“…Haggag et al showed that liposome-mediated codelivery with Ran-RCC1 inhibitory peptide could improve the antitumor effect of doxorubicin in tumor-bearing mice [ 24 ]. A previous study found that downregulation of RCC1 could sensitize immunotherapy by upregulating PD-L1 via the p27kip1/CDK4 pathway in non-small cell lung cancer, and the expression of RCC1 was inversely related to the amount of immune cell infiltration [ 18 ]. It was also reported that RCC1 promotes doxorubicin resistance in colorectal carcinoma cells [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

“…A tissue microarray showed that the expression of RCC1 was significantly associated with a longer overall survival of patients with low-grade B-cell lymphoma [ 17 ]. However, a survival analysis showed the opposite result: high expression of RCC1 was associated with a poor prognosis of non-small cell lung cancer [ 18 ]. All of these results indicate that the differential expression and function of RCC1 may depend on the type of tumor.…”

Section: Introductionmentioning

confidence: 99%

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RCC1 Expression as a Prognostic Marker in Colorectal Liver Oligometastases

Deng¹,

Lan²,

Zhao³

et al. 2021

Pathol. Oncol. Res.

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Introduction: Regulator of chromatin condensation 1 (RCC1) is a major guanine-nucleotide exchange factor for Ran GTPase, and it plays key roles in various biological processes. Previous studies have found that RCC1 may play a role in the development of tumors, but little is known about the relationship between RCC1 and colorectal liver oligometastases (CLOs).Methods: One hundred and twenty-nine pairs of matched human CLO samples, including both primary tumor and its liver metastasis specimens, were subjected to immunohistochemistry to determine the location and expression levels of RCC1. Associations between RCC1 and survival as well as gene expression profiling were explored.Results: In this study, we first observed that RCC1 was mildly increased in CLO tumor tissues compared with normal tissues, and the localization was primarily nuclear. In addition, our study found that high RCC1 expression in liver oligometastases was an independent prognostic marker for unfavorable recurrence-free survival and overall survival (p = 0.036 and p = 0.016). Gene expression profiles generated from microarray analysis showed that RCC1 was involved in pathways including “Myc targets,” “E2F targets” and “DNA repair” pathways.Conclusion: Our data indicated that RCC1 was expressed mainly in the nucleus, and strong and significant associations were found between RCC1 expression levels and the survival of CLO patients. These findings indicated that RCC1 may play a role in CLO development.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

RCC1 Expression as a Prognostic Marker in Colorectal Liver Oligometastases

Deng¹,

Lan²,

Zhao³

et al. 2021

Pathol. Oncol. Res.

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“…In view of the current research showing that the combined use of PD-1 inhibitors (nivolumab) and CTLA4 inhibitors (ipilimumab) brings significant survival advantages for patients with renal cell carcinoma [ 38 ], the strong correlation between RCC1 and the two checkpoints indicates that it may be a powerful immunotherapy marker for KICH and KIRC. A recently conducted study in non-small cell lung cancer pointed out that downregulation of RCC1 can increase the sensitivity of immunotherapy by upregulating PD-L1 through the p27 kip1 /CDK4 axis [ 39 ]. In addition, most RCC1 positive tumors correlated with CD276 and NRP1 ( Figure 7 c).…”

Section: Discussionmentioning

confidence: 99%

Integrative and Comprehensive Pancancer Analysis of Regulator of Chromatin Condensation 1 (RCC1)

Duan

Gong

et al. 2021

IJMS

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Regulator of Chromatin Condensation 1 (RCC1) is the only known guanine nucleotide exchange factor that acts on the Ras-like G protein Ran and plays a key role in cell cycle regulation. Although there is growing evidence to support the relationship between RCC1 and cancer, detailed pancancer analyses have not yet been performed. In this genome database study, based on The Cancer Genome Atlas, Genotype-Tissue Expression and Gene Expression Omnibus databases, the potential role of RCC1 in 33 tumors’ entities was explored. The results show that RCC1 is highly expressed in most human malignant neoplasms in contrast to healthy tissues. RCC1 expression is closely related to the prognosis of a broad variety of tumor patients. Enrichment analysis showed that some tumor-related pathways such as “cell cycle” and “RNA transport” were involved in the functional mechanism of RCC1. In particular, the conducted analysis reveals the relation of RCC1 to multiple immune checkpoint genes and suggests that the regulation of RCC1 is closely related to tumor infiltration of cancer-associated fibroblasts and CD8+ T cells. Coherent data demonstrate the association of RCC1 with the tumor mutation burden and microsatellite instability in various tumors. These findings provide new insights into the role of RCC1 in oncogenesis and tumor immunology in various tumors and indicate its potential as marker for therapy prognosis and targeted treatment strategies.

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“…Other trials have found a strong and signi cant association between RCC1 expression levels and survival in patients with Colorectal Liver Oligometastases [16]. In a study of non-small cell lung cancer, knockdown of RCC1 not only signi cantly inhibited the proliferation of cancer cells but also reduced the volume and weight of tumor models after PD-L1 monoclonal antibody treatment [17].…”

Section: Introductionmentioning

confidence: 97%

Systematic Pan-cancer Analysis on the Expression and Role of RCC1/SNHG3/SNHG12

Zhang

et al. 2022

Preprint

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Regulator of chromatin condensation 1 (RCC1) is the major guanine nucleotide exchange factor of RAN GTPase, which plays a key role in various biological processes such as cell cycle and DNA damage repair. Small nucleolar RNA host gene 3 (SNHG3) and SNHG12 are long-stranded non-coding RNAs (lncRNAs) and are located on chromatin very close to the sequence of RCC1. Many studies have shown that they are aberrantly expressed in tumor tissues and can affect the proliferation and viability of cancer cells. Although the effects of RCC1/SNHG3/SNHG12 on cellular activity have been reported, respectively, their overall analysis on the pan-cancer level has not been performed. Here, we performed a comprehensive analysis of RCC1/SNHG3/SNHG12 in 33 cancers through the Cancer Genome Atlas and Gene Expression Database. The results showed that RCC1/SNHG3/SNHG12 were highly expressed in a variety of tumor tissues compared to normal tissues. The expression of RCC1/SNHG3/SNHG12 in BRCA, LGG and LIHC was associated with TP53 mutations. In addition, RCC1/SNHG3/SNHG12 expression was closely associated with the prognosis of patients with multiple tumors. Immunocorrelation analysis indicated that RCC1/SNHG3/SNHG12 showed a correlation with multiple immune cell infiltration. The results of enrichment analysis suggested that RCC1/SNHG3/SNHG12 was involved in the regulation of cell cycle, apoptosis and other pathways. We found that these effects were mainly mediated by RCC1, while the trend of SNHG3/SNHG12 regulation was also consistent with RCC1. We refer to this phenomenon as "homodomain effect". These findings provide new and comprehensive insights into the role of RCC1/SNHG3/SNHG12 in tumor development and show their potential as clinical monitoring and therapy.

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Down‐regulation of RCC1 sensitizes immunotherapy by up‐regulating PD‐L1 via p27^kip1/CDK4 axis in non‐small cell lung cancer

Cited by 16 publications

References 50 publications

RCC1 Expression as a Prognostic Marker in Colorectal Liver Oligometastases

RCC1 Expression as a Prognostic Marker in Colorectal Liver Oligometastases

Integrative and Comprehensive Pancancer Analysis of Regulator of Chromatin Condensation 1 (RCC1)

Systematic Pan-cancer Analysis on the Expression and Role of RCC1/SNHG3/SNHG12

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Down‐regulation of RCC1 sensitizes immunotherapy by up‐regulating PD‐L1 via p27kip1/CDK4 axis in non‐small cell lung cancer

Cited by 16 publications

References 50 publications

RCC1 Expression as a Prognostic Marker in Colorectal Liver Oligometastases

RCC1 Expression as a Prognostic Marker in Colorectal Liver Oligometastases

Integrative and Comprehensive Pancancer Analysis of Regulator of Chromatin Condensation 1 (RCC1)

Systematic Pan-cancer Analysis on the Expression and Role of RCC1/SNHG3/SNHG12

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Down‐regulation of RCC1 sensitizes immunotherapy by up‐regulating PD‐L1 via p27^kip1/CDK4 axis in non‐small cell lung cancer