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PMC10669966
PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma
Similarly, no association was detected between SLFN12 mRNA expression and male gender (Kruskal–Wallis test, p = 0.880).
PMC10669966
PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma
Finally, we examined whether PDE3A modulators may have efficacy in treating LPS.
PMC10669966
PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma
PDE3A and SLFN12 protein expression were first evaluated in eight LPS cell lines (Figure 4A).
PMC10669966
PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma
PDE3A- and SLFN12-coexpression was detected in two of the eight LPS cell lines, SA4 and GOT3, and in the GIST882 control cell line.
PMC10669966
PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma
We then measured, with CellTiterGlo, the effect of three PDE3A modulators (anagrelide, BAY 2666605, and DNMDP) and one PDE3A enzyme inhibitor (cilostazol) on cell viability in these cell lines.
PMC10669966
PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma
Cell viabilities decreased with all PDE3A modulators in all three cell lines (two-tailed unpaired t-test, p < 0.001) (Figure 4B).
PMC10669966
PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma
No response was observed with cilostazol, indicating that PDE3A-and SLFN12-positive LPS cell lines are affected via the PDE3A–SLFN12 complex and not by enzyme inhibition.
PMC10669966
PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma
Efficacious subtype-specific targeted therapies are currently not available for LPSs.
PMC10669966
PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma
In this study, we sought to discover novel genes that are specifically overexpressed in LPS subtypes, via a large-scale transcriptome analysis.
PMC10669966
PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma
We identified 381 genes, many of which may have a role in tumorigenesis or cancer biology pathways and, therefore, may serve as therapeutic targets in LPSs.
PMC10669966
PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma
As expected, the analysis yielded some known LPS-subtype-specific genes, but also revealed multiple genes that are linked to other cancer types.
PMC10669966
PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma
As many of these genes have been described as possibly targetable—for example PAPPA in breast cancer and TROAP in glioma —the discovery of their LPS-subtype-specificity is worth considering for further investigation.
PMC10669966
PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma
In addition to identifying individual therapeutic targets, we were interested in examining signaling pathways associated with the overexpressed genes to describe the LPS subtypes and to understand the possible mechanisms of tumorigenesis.
PMC10669966
PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma
The emerging hedgehog signaling in the DDLPS-specific pathway analysis is a compelling discovery, as targeting sonic hedgehog signaling and its key factor, GLI1, has been studied in other sarcomas .
PMC10669966
PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma
Moreover, we identified GLI1 as the most upregulated gene in DDLPS, and previous studies have also shown high expression of two GLI homologs, GLI1 and GLI2, in DDLPS .
PMC10669966
PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma
MLPS tumors have frequently been described as having an activated IGF1R/PI3K/Akt signaling pathway that is induced by the FUS-DDIT3 oncoprotein .
PMC10669966
PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma
Interestingly, a highly homologous pathway, the insulin signaling pathway, was observed as the second-most-upregulated pathway in our analysis, after the phospholipase C-mediated cascade.
PMC10669966
PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma
Almost all of the upregulated pathways in PLPS were involved in DNA replication and cell proliferation.
PMC10669966
PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma
Aberrations in cell-division-associated pathways aligns with morphological features of PLPS, which frequently exhibit a high number of mitoses and multinucleated giant cells .
PMC10669966
PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma
Further studies should be conducted to investigate whether these pathways can be targeted—for example, with cyclin-dependent kinase inhibitors.
PMC10669966
PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma
Although PDE3A was only ranked 124th on the MLPS DEG list, it caught our attention because it has been recognized in GISTs and described as potentially targetable with drugs, called PDE3A modulators, that are cytotoxic to PDE3A- and SLFN12-coexpressing cell lines .
PMC10669966
PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma
The high PDE3A expression in GISTs and cardiovascular tissue might explain why it ranked relatively low in our analysis.
PMC10669966
PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma
In addition to confirming the association between PDE3A expression and the myxoid subtype, via IHC staining, high and frequent PDE3A expression was specifically seen in the high-grade MLPS samples with a round cell phenotype.
PMC10669966
PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma
High PDE3A expression, in protein level, was also associated with male gender, but no other connections with clinical factors were observed.
PMC10669966
PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma
Our pathway analysis identified PDE3A as part of the insulin signaling pathway, which shares significant similarities with the IGF1R/PI3K/Akt pathway, driven by the commonly observed FUS-DDIT3 fusion protein in MLPS .
PMC10669966
PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma
However, further research is needed to determine if elevated PDE3A expression is associated with the fusion oncogene-driven pathway alterations.
PMC10669966
PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma
The MLPS samples also exhibited higher SLFN12 mRNA expression levels than those of the DDLPS and PLPS samples.
PMC10669966
PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma
Interestingly, most of the samples that presented PDE3A and SLFN12 mRNA expression levels that were higher than those of the GIST882 cell line belonged to the myxoid subtype.
PMC10669966
PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma
This finding is intriguing and warrants further efficacy studies of PDE3A modulators in LPS in vivo models, as these compounds may lead to an MLPS-specific targeted therapy.
PMC10669966
PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma
The study had certain limitations.
PMC10669966
PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma
As frozen tissue samples for RNA extraction were not available, we used RNA isolated from FFPE samples, in which RNA is known to be degraded.
PMC10669966
PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma
However, in a previous study, we demonstrated that the transcriptomic data derived from FFPE provide profiles that are similar to those of RNA data from fresh-frozen tissue in Merkel cell carcinoma .
PMC10669966
PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma
We were unable to find any PDE3A-positive MLPS cell lines for the study.
PMC10669966
PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma
Instead, we used two PDE3A- and SLFN12-positive LPS cell lines, GOT3 classified as a WDLPS, and SA4 with unspecified histology, which showed responses to PDE3A modulators.
PMC10669966
PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma
Therefore, an association of frequent and high PDE3A expression and the efficacy of PDE3A modulators in MLPS was not confirmed in vitro.
PMC10669966
PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma
However, other studies have shown that PDE3A- and SLFN12-expressing cell lines and xenografts of various cancer types are sensitive to PDE3A modulators, suggesting that the mechanism behind the cytotoxic effect is universal and not cell-type dependent .
PMC10669966
PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma
In conclusion, our findings suggest that LPSs, specifically MLPS tumors that coexpress PDE3A and SLFN12, may be candidates for PDE3A modulator treatment.
PMC10669966
PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma
Further in vivo experiments and optimization of PDE3A and SLFN12 diagnostics should be conducted to identify suitable patients for therapy, ultimately enabling efficient patient stratification and precision medicine in the future.
PMC10669966
PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma
In summary, we identified LPS-subtype-specific highly expressed genes, which could potentially be targeted with precision medicine.
PMC10669966
PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma
These genes are associated with the hedgehog signaling pathway in DDLPS, phospholipase C, and insulin signaling pathways in MLPS and cell proliferation pathways in PLPS.
PMC10669966
PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma
Through in vitro experiments, we observed elevated PDE3A expression correlating with high-grade myxoid samples and discovered that two LPS cell lines were responsive to PDE3A modulators.
PMC10669966
PDE3A Is a Highly Expressed Therapy Target in Myxoid Liposarcoma
Further research is required to determine whether PDE3A modulators could potentially be used as precision medicine in treating MLPS—specifically, in high-grade tumors.
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
Imatinib is the first-line targeted therapy for gastrointestinal stromal tumor (GIST), but resistance frequently occurs during treatment, limiting its efficacy and clinical application.
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
We performed high-throughput sequencing of tissue specimens from imatinib-resistant GIST patients, and identified significantly high expression of polymeric immunoglobulin receptor (PIGR) in imatinib-resistant cell lines.
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
Further investigation revealed that PIGR binds specifically to LINC00870.
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
The findings from in vitro cell functional experiments provide evidence of a strong association between LINC00870 and PIGR and the processes of proliferation and metastasis in GIST.
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
Overexpression of LINC00870 in GIST significantly inhibits the glycosylation modification and secretion of the extracellular region of PIGR, leading to immune dysregulation.
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
The inhibition of PIGR or LINC00870 effectively surmounts imatinib resistance.
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
Our study identified PIGR as a critical molecule in regulating GIST imatinib resistance and elucidated the mechanism by which PIGR promotes imatinib resistance through LINC00870 inhibition of PIGR glycosylation modifications.
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
These findings provide a new theoretical basis for blocking drug resistance and improving prognosis in GIST.Gastrointestinal stromal tumor (GIST) is a malignant gastrointestinal tract tumor originating from mesenchymal cells, often in the stomach and small intestine .
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
Unfortunately, GIST is typically resistant to conventional chemotherapy and radiotherapy, leading to a 5-year survival rate lower than 35 %, as well as a high risk of recurrence and metastasis .
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
Imatinib, a molecularly targeted drug that effectively inhibits all types of ABL tyrosine kinase activity, has achieved a breakthrough in GIST treatment, significantly improving patient survival .
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
However, the development of drug resistance during imatinib therapy is a major cause of treatment failure and relapse.
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
Thus, it is crucial to investigate the molecular mechanisms underlying imatinib resistance in GIST patients for better treatment and prognosis.
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
The development of drug resistance in tumor patients arises from intricate interactions among genetic and environmental factors.
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
Several studies have confirmed a strong association between the development of drug resistance and immune dysregulation in oncology patients .
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
PIGR exhibits expression in diverse epithelial cell types and can be induced by inflammatory factors in response to viral or bacterial infections, thereby enabling PIGR to function as an intermediary between innate and adaptive immunity [, , ].
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
Recent investigations have further revealed an upregulation of PIGR expression during the malignant transformation of epithelial cells, suggesting a plausible association between tumor drug resistance and immune dysregulation [, , ].
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
Nevertheless, the precise ramifications of aberrant PIGR expression on the surface of tumor cells in GIST patients remain elusive, warranting further elucidation.
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
In recent years, research on long-stranded non-coding RNA (lncRNA) has advanced significantly, shedding light on their crucial regulatory roles in tumorigenesis and progression.
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
These roles encompass various aspects, including: (1) participation in epigenetic regulation as molecular scaffolds or decoy molecules, broadly influencing DNA methylation and thereby contributing to tumorigenesis ; (2) involvement in gene expression regulation by serving as enhancer RNAs that activate or directly pair with DNA in the promoter region to modulate transcription factor activity and influence transcription initiation ; (3) engagement in post-transcriptional regulation processes ; (4) influence on diverse biological behaviors, such as tumorigenesis, development, invasion, and metastasis [, , ].
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
Recent investigations suggest that targeting lncRNA may hold promise as a strategy for anti-cancer therapy and has the potential to modulate the responsiveness of tumor patients to existing anti-cancer drugs [, , , ].
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
However, the precise role of lncRNA in GIST patients, particularly in the context of drug resistance, still needs to be more adequately understood.
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
In this study, we identify PIGR as a critical molecule of resistance to imatinib in GIST patients.
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
Additionally, we have investigated the biological functions of both PIGR and LINC00870 in GIST.
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
Our study elucidates the underlying mechanism through which PIGR mediates imatinib resistance in GIST patients.
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
These findings significantly contribute to our understanding of the specific mechanisms of imatinib resistance in GIST patients, and provide a novel theoretical foundation for developing innovative treatment regimens involving targeted therapy, immunotherapy, and molecular therapy.
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
Imatinib treatment-resistant GIST patient samples (cancer and paracancerous tissues) and GIST patient samples (cancer and paracancerous tissues) were obtained from Fudan University Zhongshan Hospital, Shanghai, China (Table S1).
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
This study was approved by the Clinical Research Ethics Committee of Fudan University Zhongshan Hospital.
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
Nude mice and NSG mice, female, specific-pathogen-free (SPF) grade, aged 6–8 weeks, weighing 20±2g, were procured from the Experimental Animal Center of Shanghai Cancer Institute (Shanghai, China).
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
The GIST cell lines GIST-T1 and GIST-882 were obtained from the American Type Culture Collection (ATCC, Manassas, VA, USA).
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
Logarithmic growth phase cells were harvested and adjusted to a concentration of 1 × 10ˆ6/ml in serum-free culture medium.
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
Subsequently, each nude mouse was intravenously inoculated with 0.2 ml of the cell suspension.
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
Regular observation of the mice was conducted, and approximately 8–12 weeks post-inoculation, organs were excised, fixed, embedded, and subjected to hematoxylin and eosin (HE) staining.
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
Tumor liver and lung metastases were then assessed under a microscope, and the number of metastatic lesions was quantified.
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
For the subcutaneous tumor model, logarithmic phase tumor cells GIST-882, GIST-882_PIGR_KO, or GIST-882_LINC0087_KO were collected and adjusted to a concentration of 1 × 10/ml.
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
Each NSG mouse was subcutaneously inoculated with 0.2 ml of the cell suspension.
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
Tumor measurements were conducted every three days, and tumor volume was calculated using formula V = (L × W)/2, where V represents volume, L denotes length, and W signifies width.
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
After total RNA was extracted from tumor tissues and cells, reverse transcription and relative quantitative PCR were performed following protocol from Vazyme.
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
Primers were obtained from Primerbank.
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
The nucleus and cytoplasmic RNA were isolated by nuclear-cytoplasmic separation experiment using Paris Kit (Thermo) in GIST cell lines.
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
Proteins were isolated from cells and tissues using RIPA lysate (Beyotime) and quantified by a BCA working kit (Biosharp).
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
The protein was separated by SDS-PAGE gel and electro-transferred.
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
Seal each membrane for 1.5h with 5 % skim milk.
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
After being combined and incubated with the specific antibody, the Immune response band was detected by a secondary antibody and visualized using ECL luminescent solution (Servicebio).
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
Cells were fixed in 4 % PFA for 15min and permeabilized with 0.5 % TritonX-100 for 15min at 4 °C.
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
Digoxigenin-labeled probes or control probes were mixed and cells were incubated at 55 °C for 4h.
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
The cells were washed 3 times and the specific antibodies were incubated.
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
DAPI was used to counterstain nuclear.
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
Images were observed using a microscope.
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
The GIST-882 cell line was selected for drug resistance screening, and the concentrations were set to five experimental groups of DMSO (negative control), 5 μl mol, 10 μl mol, 20 μl mol, and 40 μl mol.
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
When the cells grew to 70%–80 % confluence, the tumor cells in the rhythmic growth phase were placed in a medium containing different concentration of drugs, washed twice with PBS, replaced with a drug-free medium, and cultured routinely until the cells resumed growth.
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
After the cells grew stably and entered the logarithmic growth phase, they were passaged twice.
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
Then the screened enclosures were continued to be cultured in the medium with different concentrations of drugs and the time of action was changed accordingly.
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
After a total of 10 action times (1h, 2h, 3h, 6h, 12h, 24h, 36h, 48h, 60h, 72h) and about 6 months of culture, the cells were able to grow continuously and stably in a specific concentration of drug medium and pass-through generations.
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
Then the cells' biological characteristics and drug resistance indexes were detected after 1 month of discontinuation of drug culture.
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
SDHB was used as an indicator of drug resistance success.
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
Design sgRNAs against the promoter region or first exon start and last exon termination of the target genes (PIGR and LINC00870).
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
The sgRNA sequences with high scores were selected according to the online website (http://crispr.mit.edu/).
PMC11834037
LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications
The sgRNA forward and reverse primers were annealed to form stable double-stranded DNA and ligated to the enzymatically cleaved CRISPR-Cas9/dead Cas9 system vector and verified by sequencing.