Transcriptome Analysis of Solute Carrier-Associated Genes in Hepatocellular Carcinoma: Friend or Foe?

Wei, Wei; Xu, Rubin; Ying, Xiaomei; Chen, Liang; Lu, Xiaohuan; Tang, Qikai; Xie, Jiaheng; Yu, Hongzhu

doi:10.3389/fgene.2022.856393

Cited by 5 publications

(3 citation statements)

References 32 publications

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“…Alongside WWOX / POLE4 / HSF2BP , twelve genes from the network exhibited the expression profile that is consistent between patients and cell lines. These genes were DUSP4 ( Prabhakar et al, 2014 ), SLC36A1 ( Schaffenrath et al, 2021 ; Wei et al, 2022 ), EPB41L1 ( Han et al, 2019 ), PNMA2 ( Alhajala et al, 2018 ), YPEL3 ( Phoa et al, 2020 ), SEC11C ( Pernia et al, 2020 ), FGGY ( Salzillo et al, 2016 ; Smith et al, 2021 ), LSM2 ( Sun et al, 2022 ), IGFBP7 ( Jiang et al, 2008 ), STOML2 ( Qu et al, 2019 ; Ma et al, 2021 ), PKM ( Mukherjee et al, 2013 ; El Atat et al, 2023 ), and SYNPO ( Ning et al, 2021 ; Krishna et al, 2023 ). Some of them were shortly described in previous sections, but the possible roles of all genes are recapitulated in Figure 5A , where the results of PCA are also presented.…”

Section: Resultsmentioning

confidence: 99%

Molecular landscapes of glioblastoma cell lines revealed a group of patients that do not benefit from WWOX tumor suppressor expression

Kałuzińska-Kołat,

Kołat,

Kośla

et al. 2023

Front. Neurosci.

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IntroductionGlioblastoma (GBM) is notorious for its clinical and molecular heterogeneity, contributing to therapeutic failure and a grim prognosis. WWOX is one of the tumor suppressor genes important in nervous tissue or related pathologies, which was scarcely investigated in GBM for reliable associations with prognosis or disease progression despite known alterations. Recently, we observed a phenotypic heterogeneity between GBM cell lines (U87MG, T98G, U251MG, DBTRG-05MG), among which the anti-GBM activity of WWOX was generally corresponding, but colony growth and formation were inconsistent in DBTRG-05MG. This prompted us to investigate the molecular landscapes of these cell lines, intending to translate them into the clinical context.MethodsU87MG/T98G/U251MG/DBTRG-05MG were subjected to high-throughput sequencing, and obtained data were explored via weighted gene co-expression network analysis, differential expression analysis, functional annotation, and network building. Following the identification of the most relevant DBTRG-distinguishing driver genes, data from GBM patients were employed for, e.g., differential expression analysis, survival analysis, and principal component analysis.ResultsAlthough most driver genes were unique for each cell line, some were inversely regulated in DBTRG-05MG. Alongside driver genes, the differentially-expressed genes were used to build a WWOX-related network depicting protein–protein interactions in U87MG/T98G/U251MG/DBTRG-05MG. This network revealed processes distinctly regulated in DBTRG-05MG, e.g., microglia proliferation or neurofibrillary tangle assembly. POLE4 and HSF2BP were selected as DBTRG-discriminating driver genes based on the gene significance, module membership, and fold-change. Alongside WWOX, POLE4 and HSF2BP expression was used to stratify patients into cell lines-resembling groups that differed in, e.g., prognosis and treatment response. Some differences from a WWOX-related network were certified in patients, revealing genes that clarify clinical outcomes. Presumably, WWOX overexpression in DBTRG-05MG resulted in expression profile change resembling that of patients with inferior prognosis and drug response. Among these patients, WWOX may be inaccessible for its partners and does not manifest its anti-cancer activity, which was proposed in the literature but not regarding glioblastoma or concerning POLE4 and HSF2BP.ConclusionCell lines data enabled the identification of patients among which, despite high expression of WWOX tumor suppressor, no advantageous outcomes were noted due to the cancer-promoting profile ensured by other genes.

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Section: Resultsmentioning

confidence: 99%

Molecular landscapes of glioblastoma cell lines revealed a group of patients that do not benefit from WWOX tumor suppressor expression

Kałuzińska-Kołat,

Kołat,

Kośla

et al. 2023

Front. Neurosci.

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“…Breast cancer is also known as a “cold” tumor [ 38 ]. It is necessary to explore the tumor microenvironment of breast cancer to identify differences in levels of immune cell infiltration and to identify the expression of immune checkpoint genes [ 39 ]. Our study analyzed the immune microenvironment of high-risk and low-risk breast cancer patients, which is valuable for us to carry out immunotherapy based on this signature.…”

Section: Discussionmentioning

confidence: 99%

The role of ATP binding cassette (ABC) transporters in breast cancer: Evaluating prognosis, predicting immunity, and guiding treatment

Yuan,

Xiang,

Xia

et al. 2023

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Breast cancer is currently the most prevalent form of cancer worldwide. Nevertheless, there remains limited clarity regarding our understanding of the tumor microenvironment and metabolic characteristics associated with it. ATP-binding cassette (ABC) transporters are the predominant transmembrane transporters found in organisms. Therefore, it is essential to investigate the role of ABC transporters in breast cancer. Transcriptome data from breast cancer patients were downloaded from the TCGA database. ABC transporter-related genes were obtained from the Genecards database. By LASSO regression, ABC-associated prognostic signature was constructed in breast cancer. Subsequently, immune microenvironment analysis was performed. Finally, cell experiments were performed to verify the function of ABCB7 in the breast cancer cell lines MDA-MB-231 and MCF-7. Using the ABC transporter-associated signature, we calculated a risk score for each breast cancer patient. Patients with breast cancer were subsequently categorized into high-risk and low-risk groups, utilizing the median risk score as the threshold. Notably, patients in the high-risk group exhibited significantly worse prognosis ( P <0.05). Additionally, differences were observed in terms of immune cell infiltration levels, immune correlations, and gene expression of immune checkpoints between the two groups. Functional experiments conducted on breast cancer cell lines MDA-MB-231 and MCF-7 demonstrated that ABCB7 knockdown significantly diminished cell activity, proliferation, invasion, and migration. These findings emphasize the significance of understanding ABC transporter-mediated metabolic and transport characteristics in breast cancer, offering promising directions for further research and potential therapeutic interventions.

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“…This phenomenon is accompanied by alterations in the expression of transmembrane transporters, especially solute carrier (SLC) transporters [15,16]. The cystineglutamate antiporter, also known as system Xc(-) is one of them, and SLC7A11 (also known as xCT) serves as its catalytic subunit [17]. This subunit imports cystine to synthesize glutathione (GSH), a crucial antioxidant peptide for detoxifying phospholipid hydroperoxides.…”

Section: Introductionmentioning

confidence: 99%

SLC7A11 in hepatocellular carcinoma: potential mechanisms, regulation, and clinical significance

2024

Am J Cancer Res

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Exploring novel early detection biomarkers and developing more efficacious treatments remain pressing tasks in the current research landscape for hepatocellular carcinoma (HCC). Morphologically and molecularly separate from apoptosis, cell death, and autophagy, ferroptosis is a recently discovered, unique, controlled form of cell death. SLC7A11 (also known as xCT) represents a subunit of the cystine-glutamate antiporter (also known as system Xc(-)). A growing body of research suggests that induction of ferroptosis through SLC7A11 can effectively eliminate hepatocellular carcinoma (HCC) cells, particularly those exhibiting resistance to alternative forms of cell death. Thus, targeting ferroptosis via SLC7A11 may become a new direction for the design of therapeutic strategies for HCC. Although many research articles have investigated the possible roles of SLC7A11 in HCC, a study that summarizes the main findings, including the regulators and mechanisms of action of SLC7A11 in HCC is not available. Therefore, we present a comprehensive overview of the functions of ferroptosis, particularly SLC7A11, in the identification, development, and management of HCC in this review. In addition, we discuss how this knowledge can be translated into treatment by providing a systemic therapy in advanced HCC using sorafenib, the first-line drug targeting multiple kinases and SLC7A11. We further dissect the possible barriers as well as the corresponding solutions and provide insights on how to navigate effective treatment using this knowledge.

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Transcriptome Analysis of Solute Carrier-Associated Genes in Hepatocellular Carcinoma: Friend or Foe?

Cited by 5 publications

References 32 publications

Molecular landscapes of glioblastoma cell lines revealed a group of patients that do not benefit from WWOX tumor suppressor expression

Molecular landscapes of glioblastoma cell lines revealed a group of patients that do not benefit from WWOX tumor suppressor expression

The role of ATP binding cassette (ABC) transporters in breast cancer: Evaluating prognosis, predicting immunity, and guiding treatment

SLC7A11 in hepatocellular carcinoma: potential mechanisms, regulation, and clinical significance

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