Kaisa Cui

Wuxi Fourth People's Hospital

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Youjun Li

Henan University of Science and Technology

Zhaohui Huang

Wuxi Fourth People's Hospital

Edward V. Prochownik

UPMC Hillman Cancer Center

Bojian Fei

Jiangnan University

Xi Lin

Wenzhou Medical University

Yahui Zhu

Sichuan University

Gu Li

New York University Shanghai

Shengbai Sun

Zhejiang University

Yajun Li

Guangdong Provincial People's Hospital

Chaoqun Li

Gansu Agricultural University

Cooperative Institutions

Wuhan University

Jiangnan University

Wuxi Fourth People's Hospital

Sun Yat-sen University

Chinese Academy of Medical Sciences & Peking Union Medical College

Chinese Academy of Sciences

Huazhong University of Science and Technology

Zhongnan Hospital of Wuhan University

Fudan University

Renmin Hospital of Wuhan University

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Ferroptosis and the tumor microenvironment

Journal of Experimental & Clinical Cancer Research (2024)

Kaisa Cui Kang Wang Zhaohui Huang

Abstract Ferroptosis is a type of regulated cell death characterized by its non-apoptotic, iron-dependent and oxidative nature. Since its discovery in 2012, extensive research has demonstrated its pivotal roles in tumorigenesis, metastasis and cancer therapy. The tumor microenvironment (TME) is a complex ecosystem comprising cancer cells, non-cancer cells, extracellular matrix, metabolites and cytokines. Recent studies have underscored a new paradigm in which non-cancer cells in the TME, such as immune and stromal cells, also play significant roles in regulating tumor progression and therapeutic resistance typically through complicated crosstalk with cancer cells. Notably, this crosstalk in the TME were partially mediated through ferrotopsis-related mechanisms. This review provides a comprehensive and systematic summary of the current findings concerning the roles of ferroptosis in the TME and how ferroptosis-mediated TME reprogramming impacts cancer therapeutic resistance and progression. Additionally, this review outlines various ferroptosis-related therapeutic strategies aimed at targeting the TME.

Crosstalk

Reprogramming

Tumor progression

10.1186/s13046-024-03235-0

Cite

Citations (1)

Hsa_Circ_0062682 Promotes Serine Metabolism and Tumor Growth in Colorectal Cancer by Regulating the miR-940/PHGDH Axis

SSRN Electronic Journal (2021)

Shengbai Sun Chaoqun Li Kaisa Cui Bingxin Liu Mingyue Zhou

Background: Colorectal cancer (CRC) is one of the most common malignancy globally. Increasing evidences indicate that circular RNAs (circRNAs) play a pivotal role in various cancers.Methods: Differential circRNAs were determined by edgeR package. The expression of circ_0062682, miR-940 and PHGDH were analyzed by qRT-PCR. We used in vitro proliferation assays and in vivo xenograft model to evaluate the tumorigenic features of CRC cells. Abundance of serine were measured by liquid chromatography mass spectrometry assay.Findings: Increased expression of circ_0062682 in CRC notably correlated with a poorly prognosis and advanced tumor stage. Functional experiments showed that circ_0062682 knockdown reduced CRC growth both in vitro and in vivo. Mechanistically, we revealed that circ_0062682 could sponge miR-940 and identified that PHGDH, a key oxidoreductase involving in serine biosynthesis, as a novel target of miR-940. The expression of PHGDH was downregulated in circ_0062682–depleted or miR-940 overexpressing CRC cells at both mRNA and protein levels.Interpretation: Circ_0062682 promotes serine metabolism and tumor growth in CRC by regulating the miR-940/PHGDH axis, suggesting circ_0062682 as a potential novel therapeutic target for CRC.Funding: This study was partially supported by grants from the National Natural Science Foundation of China (81972220 and 82002964), Medical Key Professionals Program of Jiangsu Province (ZDRCB2016017), Wuxi Medical Innovation Team (CXTP003), and Medical Leading Talents of Wuxi Taihu Lake Talent Plan.Declaration of Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.Ethics Approval Statement: Our study was approved by the Research Ethics Committee of Affiliated Hospital of Jiangnan University.

10.2139/ssrn.3914627

Cite

Citations (0)

Identification of an immune overdrive high-risk subpopulation with aberrant expression of FOXP3 and CTLA4 in colorectal cancer

Oncogene (2021)

Kaisa Cui Surui Yao Han Zhang Mingyue Zhou Bingxin Liu

TIGIT

Subtyping

10.1038/s41388-021-01677-w

Cite

Citations (19)

Supplementary Figure S2 from Amplification of Glyceronephosphate O-Acyltransferase and Recruitment of USP30 Stabilize DRP1 to Promote Hepatocarcinogenesis

Gu Li Yahui Zhu Xi Lin Yajun Li Kaisa Cui

<p>Supplementary Figure S2 shows that GNPAT interacts with DRP1 to regulate mitochondrial morphology.</p>

10.1158/0008-5472.22420244.v1

Cite

Citations (0)

Hsa_circ_0062682 Promotes Serine Metabolism and Tumor Growth in Colorectal Cancer by Regulating the miR-940/PHGDH Axis

Frontiers in Cell and Developmental Biology (2021)

Shengbai Sun Chaoqun Li Kaisa Cui Bingxin Liu Mingyue Zhou

Colorectal cancer (CRC) is one of the most common malignancies globally. Increasing evidence indicates that circular RNAs (circRNAs) play a pivotal role in various cancers. The present study focused on exploring the role of a functionally unknown circRNA, hsa_circ_0062682 (circ_0062682), in CRC. By online analyses and experimental validations, we showed that circ_0062682 expression was aberrantly increased in CRC tissues compared with paired normal tissues. Increased expression of circ_0062682 in CRC notably correlated with a poor prognosis and advanced tumor stage. Functional experiments showed that circ_0062682 knockdown reduced CRC growth both in vitro and in vivo. Mechanistically, we revealed that circ_0062682 could sponge miR-940 and identified D-3-phosphoglycerate dehydrogenase (PHGDH), a key oxidoreductase involved in serine biosynthesis, as a novel target of miR-940. Silencing miR-940 expression could mimic the inhibitory effect of circ_0062682 knockdown on CRC proliferation. The expression of PHGDH was downregulated in circ_0062682-depleted or miR-940 overexpressing CRC cells at both the mRNA and protein levels. Circ_0062682 knockdown suppressed CRC growth by decreasing PHGDH expression and serine production via miR-940. Taken together, these data demonstrate, for the first time, that circ_0062682 promotes serine metabolism and tumor growth in CRC by regulating the miR-940/PHGDH axis, suggesting circ_0062682 as a potential novel therapeutic target for CRC.

10.3389/fcell.2021.770006

Cite

Citations (15)

Ferroptosis-Associated Molecular Features to Aid Patient Clinical Prognosis and Therapy Across Human Cancers

Frontiers in Immunology (2022)

Kaisa Cui Liang Gong Kang Wang Yuanben Wang Liuying Huang

Ferroptosis is a new non-apoptotic form that regulates cell death and is mainly dependent on iron-mediated oxidative damage and subsequent cell membrane damage. Ferroptosis may be a potential therapeutic strategy for immunotherapy, chemotherapy, and radiotherapy in human cancers. Numerous studies have analyzed ferroptosis-correlated signatures or genes, but a systematic landscape of associations among tumor ferroptosis, clinical outcomes, tumor microenvironment, and therapies in human cancers is lacking. Here, we developed a relative ferroptosis level (RFL) combined with drive/suppress regulators and validated it in the Gene Expression Omnibus datasets of ferroptotic drug treatment. Based on this effective evaluation method, we classified about 7,000 tumor samples into high and low RFL groups in each cancer type and observed that high RFL cases demonstrate favorable survival outcomes in nine cancer types from The Cancer Genome Atlas. Then, several RFL-correlated candidate genes that have not been reported to be ferroptosis-related were selected and experimentally validated in five cancer cell lines using Erastin treatment. We further showed that both immunostimulatory and immunosuppressive phenotypes were observed in high RFL tumors, suggesting that the consideration of ferroptosis could be a potential strategy in cancer immunotherapy. Moreover, we found that high RFL cases/cells showed responder or sensitivity to chemotherapy and radiotherapy. Our study provides a comprehensive molecular-level understanding of ferroptosis and may have practical implications for clinical cancer therapies, including immunotherapy, chemotherapy, and radiotherapy.

10.3389/fimmu.2022.888757

Cite

Citations (3)

Comprehensive Characterization of Integrin Subunit Genes in Human Cancers

Frontiers in Oncology (2021)

Kaisa Cui Xiaohan Wu Liang Gong Surui Yao Shengbai Sun

Although integrin subunit genes (ITGs) have been reported to be associated with some human cancer types, a systematic assessment of ITGs across human cancers is lacking. Hence, we performed comprehensive analyses to investigate mRNA expression, copy number variation (CNV), DNA methylation, mutation, and clinical landscapes of ITGs in more than 8000 cancer patients from The Cancer Genome Atlas (TCGA) dataset. Landscapes of ITGs were established across 20 human cancer types. We observed that ITGs are extensively dysregulated with heterogeneity in different system cancer types, part of which are driven by CNV, DNA hypomethylation or mutation. Furthermore, dysregulated prognosis-related ITGs were systematically identified in each cancer type, including ITGA11 in stomach adenocarcinoma (STAD). The models based on dysregulated ITGs with clinical relevance and TNM staging indexes are good indicators in STAD and head and neck squamous cell carcinoma. Finally, ITGA11 is overexpressed and associated with poor survival in STAD cases from the TCGA and additionally Gene Expression Omnibus cohorts. Functionally, ITGA11 knockdown inhibits malignant phenotypes in STAD cell lines AGS and MKN45, demonstrating the oncogenic role of ITGA11 in STAD. Together, this study highlights the important roles of ITGs in tumorigenesis as potential prognostic biomarkers, and provide an effective resource that identifies cancer-related genes of ITGs in human cancers.

10.3389/fonc.2021.704067

Cite

Citations (9)

Amplification of Glyceronephosphate O-Acyltransferase and Recruitment of USP30 Stabilize DRP1 to Promote Hepatocarcinogenesis

Cancer Research (2018)

Li Gu Yahui Zhu Xi Lin Yajun Li Kaisa Cui

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, and the underlying pathophysiology of HCC is highly complex. In this study, we report that, in a bioinformatic screen of 2,783 genes encoding metabolic enzymes, GNPAT, which encodes the enzyme glyceronephosphate O-acyltransferase, is amplified, upregulated, and highly correlated with poor clinical outcome in human patients with HCC. High GNPAT expression in HCC was due to its amplification and transcriptional activation by the c-Myc/KDM1A complex. GNPAT compensated the oncogenic phenotypes in c-Myc-depleted HCC cells. Mechanistically, GNPAT recruited the enzyme USP30, which deubiquitylated and stabilized dynamin-related protein 1 (DRP1), thereby facilitating regulation of mitochondrial morphology, lipid metabolism, and hepatocarcinogenesis. Inhibition of GNPAT and DRP1 dramatically attenuated lipid metabolism and hepatocarcinogenesis. Furthermore, DRP1 mediated the oncogenic phenotypes driven by GNPAT. Taken together, these results indicate that GNPAT and USP30-mediated stabilization of DRP1 play a critical role in the development of HCC.Significance: This study identifies and establishes the role of the enzyme GNPAT in liver cancer progression, which may serve as a potential therapeutic target for liver cancer. Cancer Res; 78(20); 5808-19. ©2018 AACR.

10.1158/0008-5472.can-18-0340

Cite

Citations (44)

Acetylation of aldehyde dehydrogenase ALDH1L2 regulates cellular redox balance and the chemosensitivity of colorectal cancer to 5-fluorouracil

Journal of Biological Chemistry (2023)

Chaoqun Li Peng Teng Shengbai Sun Kaisa Cui Surui Yao

Folate-mediated one-carbon metabolism (FOCM) is crucial in sustaining rapid proliferation and survival of cancer cells. The folate cycle depends on a series of key cellular enzymes, including aldehyde dehydrogenase 1 family member L2 (ALDH1L2) that is usually overexpressed in cancer cells, but the regulatory mechanism of ALDH1L2 remains undefined. In this study, we observed the significant overexpression of ALDH1L2 in colorectal cancer (CRC) tissues, which is associated with poor prognosis. Mechanistically, we identified that the acetylation of ALDH1L2 at the K70 site is an important regulatory mechanism inhibiting the enzymatic activity of ALDH1L2 and disturbing cellular redox balance. Moreover, we revealed that sirtuins 3 (SIRT3) directly binds and deacetylates ALDH1L2 to increase its activity. Interestingly, the chemotherapeutic agent 5-fluorouracil (5-Fu) inhibits the expression of SIRT3 and increases the acetylation levels of ALDH1L2 in colorectal cancer cells. 5-Fu-induced ALDH1L2 acetylation sufficiently inhibits its enzymatic activity and the production of NADPH and GSH, thereby leading to oxidative stress-induced apoptosis and suppressing tumor growth in mice. Furthermore, the K70Q mutant of ALDH1L2 sensitizes cancer cells to 5-Fu both in vitro and in vivo through perturbing cellular redox and serine metabolism. Our findings reveal an unknown 5-Fu-SIRT3-ALDH1L2 axis regulating redox homeostasis, and suggest that targeting ALDH1L2 is a promising therapeutic strategy to sensitize tumor cells to chemotherapeutic agents.

SIRT3

10.1016/j.jbc.2023.105090

Cite

Citations (7)

Long Noncoding RNA DLGAP1-AS2 Promotes Tumorigenesis and Metastasis by Regulating the Trim21/ELOA/LHPP Signaling Axis in Colorectal Cancer

Research Square (Research Square) (2022)

Xue Wang J. Zhao Han Cheng Jiuming Li Ying Chen

Abstract Background: Long noncoding RNAs (lncRNAs) have driven research focused on their effects as oncogenes or tumor suppressors involved in carcinogenesis. However, the functions and mechanisms of most lncRNAs in colorectal cancer (CRC) remain unclear. Methods: The expression of DLGAP1-AS2 was assessed by quantitative RT-PCR in multiple CRC cohorts. The impacts of DLGAP1-AS2 on CRC growth and metastasis were evaluated by a series of in vitro and in vivo assays. Furthermore, the underlying mechanism of DLGAP1-AS2 in CRC was revealed by RNA pull down, RNA immunoprecipitation, RNA sequencing, luciferase assays, chromatin immunoprecipitation, and rescue experiments. Results: We discovered that DLGAP1-AS2promoted CRC tumorigenesis and metastasis by physically interacting with Elongin A (ELOA) and inhibiting its protein stability by promoting tripartite motif containing 21(Trim21)-mediated ubiquitination modification and degradation of ELOA. In particular, we revealed that DLGAP1-AS2decreases phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) expression by inhibiting ELOA-mediated transcriptional activating of LHPP and thus blocking LHPP-dependent suppression of the AKT signaling pathway. In addition, we also demonstrated that DLGAP1-AS2 was bound and stabilized by cleavage and polyadenylation specificity factor (CPSF2) and cleavage stimulation factor (CSTF3). Conclusions: The discovery of DLGAP1-AS2, a promising prognostic biomarker, reveals a new dimension into the molecular pathogenesis of CRC and provides a prospective treatment target for this disease. Keywords: colorectal cancer, DLGAP1-AS2, ELOA, Trim21, LHPP

Chromatin immunoprecipitation

Immunoprecipitation

10.21203/rs.3.rs-1295312/v1

Cite

Citations (0)