Journal: Cancer letters

Article Title: YBX1 as a therapeutic target to suppress the LRP1-β-catenin-RRM1 axis and overcome gemcitabine resistance in pancreatic cancer.

doi: 10.1016/j.canlet.2024.217197

Figure Lengend Snippet: Fig. 1. YBX1 is highly expressed in pancreatic cancer and is associated with high malignancy and poor prognosis. (A) Differences in gene expression at the transcriptional level between the gemcitabine-resistant and -sensitive groups. (B) YBX1 expression in PDAC based on TCGA database. (C) Overall survival (OS) analysis based on TCGA database showed that patients with higher YBX1 expression had worse prognosis. (D) Scoring of specimens with different staining intensities in TMA. (E) YBX1 expression was significantly higher in tumor tissues (T) than that in para-cancer tissues (TP). (F) YBX1 expression was positively correlated with malignancy. (G) OS analysis based on TMA showed that patients with higher YBX1 expression had a worse prognosis.

Article Snippet: Gemcitabine and the YBX1 pathway inhibitor SU056 were purchased from Selleckchem.

Techniques: Gene Expression, Expressing, Staining

Journal: Cancer letters

Article Title: YBX1 as a therapeutic target to suppress the LRP1-β-catenin-RRM1 axis and overcome gemcitabine resistance in pancreatic cancer.

doi: 10.1016/j.canlet.2024.217197

Figure Lengend Snippet: Fig. 2. YBX1 promotes pancreatic cancer in both in vivo and in vitro models. (A and B) The YBX1 stable transcripts of MIA PaCa-2 and PANC-1 were verified using qRT-PCR and western blotting. (C) Validation of YBX1 expression in stable transcripts using immunofluorescence. (D–G) Effect of knockdown of YBX1 on clone formation, proliferative capacity, scratch test, and Transwell assay in pancreatic cancer cells. (H) Effects of YBX1 knockdown on subcutaneous pancreatic cancer cell tumor formation in nude mice.

Article Snippet: Gemcitabine and the YBX1 pathway inhibitor SU056 were purchased from Selleckchem.

Techniques: In Vivo, In Vitro, Quantitative RT-PCR, Western Blot, Biomarker Discovery, Expressing, Immunofluorescence, Knockdown, Transwell Assay

Journal: Cancer letters

Article Title: YBX1 as a therapeutic target to suppress the LRP1-β-catenin-RRM1 axis and overcome gemcitabine resistance in pancreatic cancer.

doi: 10.1016/j.canlet.2024.217197

Figure Lengend Snippet: Fig. 3. YBX1 knockdown enhances the gemcitabine sensitivity of pancreatic cancer cells. (A) Morphological changes in the YBX1 knockdown groups of MIA PaCa-2 and PANC-1 cells in the presence of gemcitabine were more pronounced than those in the control group. (B) In the clone-formation assay, low-dose (30 nM) gemcitabine was significantly inhibited in the YBX1 knockdown group. (C) In three different patient-derived (patient 1/2/3) organoid models, low-dose (20 nM) gemcitabine was significantly more potent in killing the YBX1 knockdown group than the control group. (D) Determination of IC50 of gemcitabine in knockdown groups of MIA PaCa-2 and PANC-1. (E) Detection of apoptosis levels in PANC-1 knockdown and control groups before and after the addition of gemcitabine.

Article Snippet: Gemcitabine and the YBX1 pathway inhibitor SU056 were purchased from Selleckchem.

Techniques: Knockdown, Control, Tube Formation Assay, Derivative Assay

Journal: Cancer letters

Article Title: YBX1 as a therapeutic target to suppress the LRP1-β-catenin-RRM1 axis and overcome gemcitabine resistance in pancreatic cancer.

doi: 10.1016/j.canlet.2024.217197

Figure Lengend Snippet: Fig. 4. Transcriptome sequencing clustering reveals Wnt/β-catenin pathway and the key downstream molecule LRP1. (A) Cross-analysis of genes down regulated in the two YBX1 knockout groups yielded a total of 239 common genes. (B) Pathway clustering of the differential genes revealed the involvement of the Wnt/β-catenin pathway. (C) Differential mRNA expression of Wnt/β-catenin pathway genes in different YBX1 expression groups. (D) Differences in the expression of LRPs between the YBX1 knockdown and control groups. (E) Correlation between YBX1 and LRP1 at the transcriptional level in TCGA and GTEx databases. (F) Altered expression of LRP1 and β-catenin verified by IHC staining of subcutaneous tumor blocks in mice.

Article Snippet: Gemcitabine and the YBX1 pathway inhibitor SU056 were purchased from Selleckchem.

Techniques: Sequencing, Knock-Out, Expressing, Knockdown, Control, Immunohistochemistry

Journal: Cancer letters

Article Title: YBX1 as a therapeutic target to suppress the LRP1-β-catenin-RRM1 axis and overcome gemcitabine resistance in pancreatic cancer.

doi: 10.1016/j.canlet.2024.217197

Figure Lengend Snippet: Fig. 5. YBX1 promotes LRP1 transcription by binding to the LRP1 promoter region and significantly alters the content and distribution of β-catenin in pancreatic cancer cells. (A and B) Changes in LRP1 at the mRNA and protein levels after YBX1 knockdown in MIA PaCa-2 and PANC-1 cells. (C) LRP1 expression was altered in the YBX1 knockdown group. (D) Dual luciferase validation of YBX1 for promoting LRP1 transcription. (E) ChIP validates direct binding of YBX1 to the LRP1 promoter region. (F) β-catenin decreases with YBX1 knockdown at the protein level in MIA PaCa-2 and PANC-1 cells. (G) LRP1 expression and distribution was altered in the YBX1 knockout groups.

Article Snippet: Gemcitabine and the YBX1 pathway inhibitor SU056 were purchased from Selleckchem.

Techniques: Binding Assay, Knockdown, Expressing, Luciferase, Biomarker Discovery, Knock-Out

Journal: Cancer letters

Article Title: YBX1 as a therapeutic target to suppress the LRP1-β-catenin-RRM1 axis and overcome gemcitabine resistance in pancreatic cancer.

doi: 10.1016/j.canlet.2024.217197

Figure Lengend Snippet: Fig. 6. β-catenin binds to the promoter region of RRM1, a key gene for gemcitabine resistance, via TCF7L1, and thereby promotes RRM1 expression. (A) Scheme of gemcitabine metabolism in cells. (B) Analysis of the correlation between genes related to gemcitabine metabolism and YBX1 in TCGA database. (C and D) Changes in the mRNA and protein levels of RRM1 after YBX1 knockdown in MIA PaCa-2 and PANC-1 cells. (E) ChIP validates direct binding of TCF3 to the LRP1 promoter region. (F) Dual luciferase validation of TCF3 regulation of LRP1 transcription.

Article Snippet: Gemcitabine and the YBX1 pathway inhibitor SU056 were purchased from Selleckchem.

Techniques: Expressing, Knockdown, Binding Assay, Luciferase, Biomarker Discovery

Journal: Cancer letters

Article Title: YBX1 as a therapeutic target to suppress the LRP1-β-catenin-RRM1 axis and overcome gemcitabine resistance in pancreatic cancer.

doi: 10.1016/j.canlet.2024.217197

Figure Lengend Snippet: Fig. 7. YBX1 inhibitor SU056 enhances the inhibitory effect of gemcitabine on pancreatic cancer in vivo and in vitro. (A) Effects of 100 nM SU056 and 50 nM gemcitabine alone, and in combination, in organoids. (B) Changes in IC50 in MIA PaCa-2 and PANC-1 when gemcitabine is combined with SU056. (C) Changes in the apoptosis level in MIA PaCa-2 and PANC-1 when gemcitabine is combined with SU056. (D) Effect of intraperitoneal injection of 20 mg/kg SU056 and 10 mg/kg gemcitabine alone or in combination on subcutaneous tumor formation in nude mice.

Article Snippet: Gemcitabine and the YBX1 pathway inhibitor SU056 were purchased from Selleckchem.

Techniques: In Vivo, In Vitro, Injection