Fig. 1: Oncostatin M (OSM) receptor is upregulated in chemoresistant ovarian cancer through OSMR heterodimerization. | npj Precision Oncology

Fig. 1: Oncostatin M (OSM) receptor is upregulated in chemoresistant ovarian cancer through OSMR heterodimerization.

From: Blocking Oncostatin M receptor abrogates STAT3 mediated integrin signaling and overcomes chemoresistance in ovarian cancer

Fig. 1

a Volcano plot shows differentially expressed genes in OVCAR8-CisR (cisplatin resistant) spheroids (N = 4) compared with OVCAR8 sensitive spheroids (N = 4) in GSE45553 microarray dataset. Significance threshold is P ≤ 0.05 and Log2 (fold change) threshold set at ±0.585 on both sides. Top hits and OSM module genes are labeled (P value < 0.05, FDR < 0.1). ns non-significant. b Ingenuity Pathway Analysis (IPA) shows canonical pathways that are >1.5-fold change in OVCAR8-CisR spheroids (GSE45553) with a threshold cut off log10 (fold change) > 4 respectively. c Correlation graph shows Spearman’s correlation of OSMR with (left panel) Integrin family genes and (right panel) with integrins α and β genes exhibiting P value ≤ 0.05 in TCGA ovarian cancer cohort (n = 379) dataset downloaded from GDC data portal. d Volcano plot shows differentially expressed genes in A2780 CisR cell line compared with A2780 sensitive cell lines in triplicates in the qPCR array panel of IL6 signaling. Genes were selected based on P value ≤ 0.05 and Log2 (fold change) threshold set at +/−0.58 in both directions. ns: non-significant. e Total RNA was isolated from the indicated cell lines and mRNA expression of IL6 receptor family genes were determined. β-actin gene was used as an internal standard. f Western blot shows OSMR and IL6ST expression in the lysates of a set of cisplatin-sensitive and resistant ovarian cancer cell lines. g OSMR was immunoprecipitated (IP) from A2780-CisR and A2780 sensitive cells were treated with recombinant human OSM (100 ng/mL) and crosslinked with BS3 agent. Monomers and dimers obtained by IP were resolved on SDS-PAGE and immunoblotted using OSMR and IL6ST specific antibodies. h Western blot shows the level of OSMR, and total and phosphorylated form of STAT3 in both cisplatin sensitive and resistant version of A2780 and OVCAR8 cells. Student’s t test (two tailed, unpaired) was performed to determine significance between the groups. Error bars represent mean ± SEM. ****P ≤ 0.0001, **P ≤ 0.01, *P ≤ 0.05, ns non-significant.

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