The impact of fusion genes on cancer stem cells and drug resistance

Panicker, Saurav; Venkatabalasubramanian, Sivaramakrishnan; Pathak, Surajit; Ramalingam, Satish

doi:10.1007/s11010-021-04203-4

Cited by 8 publications

(9 citation statements)

References 73 publications

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“…In other cancers, many fusion transcripts have been reported in association with drug resistance (Panicker et al, 2021), and it has been suggested that these fusion genes could be excellent targets to reestablish the sensitivity to chemotherapeutic drugs. In the present study, we have revealed a fusion transcript involving DHFR, a gene known to be responsible for MTX resistance, and MSH3, so far not known as drug resistance associated gene.…”

Section: Discussionmentioning

confidence: 99%

Single-nucleotide polymorphism profiling by multimodal-targeted next-generation sequencing in methotrexate-resistant and -sensitive human osteosarcoma cell lines

Casotti,

Hattinger,

Patrizio

et al. 2023

Front. Pharmacol.

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Introduction: Methotrexate (MTX) is one of the most important drugs included in the first-line protocols to treat high-grade osteosarcoma (HGOS). Although several polymorphisms have been reported to be associated with drug response or MTX-related toxicity in pharmacogenetic studies, their role in the development of MTX resistance in HGOS is still unclear.Methods: Therefore, in this study, 22 single nucleotide polymorphisms (SNPs) in 4 genes of the folate metabolism, 7 MTX transporter genes, and 2 SNPs of the tumor protein p53 (TP53) gene were investigated using a custom multimodal-targeted next-generation sequencing (mmNGS) approach in 8 MTX-resistant and 12 MTX-sensitive human HGOS cell lines. The panel was validated by TaqMan genotyping assays.Results: High instability of TP53 rs1642785 was observed in all U-2OS/MTX variants. Allele changes of the solute carrier family 19 member 1/replication factor C subunit 1 (SLC19A1, previously known as RFC1) and rs1051266 were identified in all Saos-2/MTX-resistant variants in both DNA- and RNA- derived libraries compared to the parental Saos-2 cell line. Allele changes of methylenetetrahydrofolate reductase (MTHFR) rs1801133 were identified only in the RNA-derived libraries of the two U2OS variants with the highest MTX resistance level. Significantly upregulated gene expression associated with the development of MTX resistance was revealed for dihydrofolate reductase (DHFR) whereas SLC19A1 was downregulated. In addition, a fusion transcript of DHFR (ex4) and MutS Homolog 3 (MSH3) (ex9) was identified in the RNA libraries derived from the two U-2OS variants with the highest MTX resistance level.Conclusion: This innovative mmNGS approach enabled the simultaneous exploration of SNPs at DNA and RNA levels in human HGOS cell lines, providing evidence of the functional involvement of allele changes associated with the development of MTX resistance.

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Section: Discussionmentioning

confidence: 99%

Single-nucleotide polymorphism profiling by multimodal-targeted next-generation sequencing in methotrexate-resistant and -sensitive human osteosarcoma cell lines

Casotti,

Hattinger,

Patrizio

et al. 2023

Front. Pharmacol.

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“…After that, the collected lncRNAs were acquired to establish the SRLncSig risk score model with Lasso regression analyses. Since stemness was acknowledged as an important cause of chemotherapy resistance (Grandits and Wieser, 2021;Liu et al, 2021;Marimuthu et al, 2021;Narusaka et al, 2021;Oliveira et al, 2021;Panicker et al, 2021), the SRLncSig was firstly tested for its predictive value for chemotherapy response. Higher SRLncSig score was revealed with lower IC50, suggesting a superior chemotherapy response for the high-risk group.…”

Section: Discussionmentioning

confidence: 99%

Integrated Analysis of Stemness-Related LncRNAs Helps Predict the Immunotherapy Responsiveness of Gastric Cancer Patients

Jiang

Chen

et al. 2021

Front. Cell Dev. Biol.

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The immune microenvironment plays a critical role in tumor biology. As a critical feature of cancers, stemness is acknowledged as a contributor to the development of drug resistance in gastric cancers (GCs). Long non-coding RNAs (lncRNAs) have been revealed to participate in this process. In this study, we aimed to develop a stemness-related lncRNA signature (SRLncSig) with guiding significance for immunotherapy. Three cohorts (TCGA, Zhongshan, and IMvigor210) were enrolled for analysis. A list of stemness-related lncRNAs (SRlncRNAs) was collected by co-expression strategy under the threshold of coefficient value >0.35 and p-value < 0.05. Cox and Lasso regression analysis was further applied to find out the SRlncRNAs with prognosis-predictive value to establish the SRLncSig in the TCGA cohort. IPS and TIDE algorithms were further applied to predict the efficacy of SRLncSig in TCGA and Zhongshan cohorts. IMvigor210 was composed of patients with clinical outcomes of immunotherapy. The results indicated that SRLncSig not only was confirmed as an independent risk factor for GCs but also identified as a robust indicator for immunotherapy. The patient with a lower SRLncSig score was more likely to benefit from immunotherapy, and the results were highly consistent in three cohorts. In conclusion, our study not only could clarify the correlations between stemness and immunotherapy in GC patients but also provided a model to guide the applications of immunotherapy in clinical practice.

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“…Recently, the occurrence of gene fusion has been shown to contribute to carcinogenesis by influencing CSC. [ 84 ] Gene fusion is a genetic process that creates a new distinctive gene from two separate genes and is known to have a role in tumorigenesis and the spread of cancer. As a result, it has been used as a both predictive and diagnostic biomarker for several cancers and as a suitable therapeutic target in cancer therapy.…”

Section: Cd63 and Gene Fusionmentioning

confidence: 99%

“…[ 76 ] Targeting CD63 gene fusion could be an alternative approach for cancer therapy, as CSC harboring gene fusion has been reported to be more aggressive. [ 84 ] The various approaches defining the potency of CD63 as a theragnostic target have been demonstrated in Figure 7 . All these findings suggest that this particular membrane protein molecule can prove to be an effective cancer theragnostic molecule in the coming future.…”

Section: Cd63 As Potential Theragnostic Targetmentioning

confidence: 99%

Revisiting the Role of CD63 as Pro‐Tumorigenic or Anti‐Tumorigenic Tetraspanin in Cancers and its Theragnostic Implications

2023

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Cluster of differentiation antigen 63 (CD63) belongs to a superfamily of proteins, usually defined as tetraspanins which are known to transverse the bilayer membranes four times. The expression of CD63 has been shown to get altered in several cancers, where it has been demonstrated to act as both a tumor promoter and tumor suppressor. The present review describes the mechanism of how CD63 promotes tumor formation in certain cancer types while inhibiting in some other specific cancers. Glycosylation, a post-translational process plays a significant role in regulating the expression and function of these membrane proteins. Being a crucial exosomal flag protein, CD63 has been found to get involved in endosomal cargo sorting as well as the production of extracellular vesicles. Increased expression of exosomal CD63 derived from advanced tumors has demonstrated its role in promoting metastasis. CD63 also regulates the characteristic and function of stem cells on which they get expressed. This particular tetraspanin has been discovered to participate in gene fusion to perform distinctive roles in certain specific cancer types like breast cancer and pigmented epithelioid melanocytoma. Furthermore, this review mentions twelve different microRNAs obtained from miRDB that might target CD63. A few theragnostic uses of this membrane protein are also discussed. Thereby, the review indicates that further studies on CD63 might prove it to be an effective therapeutic target in different cancers in the coming future.

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The impact of fusion genes on cancer stem cells and drug resistance

Cited by 8 publications

References 73 publications

Single-nucleotide polymorphism profiling by multimodal-targeted next-generation sequencing in methotrexate-resistant and -sensitive human osteosarcoma cell lines

Single-nucleotide polymorphism profiling by multimodal-targeted next-generation sequencing in methotrexate-resistant and -sensitive human osteosarcoma cell lines

Integrated Analysis of Stemness-Related LncRNAs Helps Predict the Immunotherapy Responsiveness of Gastric Cancer Patients

Revisiting the Role of CD63 as Pro‐Tumorigenic or Anti‐Tumorigenic Tetraspanin in Cancers and its Theragnostic Implications

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