Fig. 7

miR-1 modulates the CXCR4/FOXM1/RRM2 axis and enhances survival. A Representative H&E and IHC of serial sections of same liver tissue having metastasis for CXCR4, FOXM1, and RRM2 from SBC5 no miR-1(-DOX-Off) and + miR-1 (+ DOX-On) intracardiac xenografts. Image of whole liver tissue sections having metastasis with an area highlighted with a box provided in higher-magnification or zoom inset. Scale bars represent 1 mm (with successive magnification). B IHC quantification for respective proteins was presented in the right panels (n = 6 liver sections). C Representative H&E and IHC of the same liver tissue having metastasis for CXCR4, FOXM1, and RRM2 from intracardiac xenografts of SBC3 and SBC3-miR-1Zip cells. Scale bars represent 400 µm (with successive magnification). D IHC quantification for respective proteins was presented in the right panels (n = 6 liver sections). E Kaplan–Meier survival analysis of NSG mice bearing metastatic SCLC xenografts under no miR-1 and + miR-1 conditions for 24 weeks (n = 10 mice in each group). F Violin with point graph representing the quantitative expression of serum miR-1 in -DOX-Off/ + DOX-On group of NSG mice. Statistical significance was calculated using two-tailed Student’s t-test for unpaired samples, where ***, p < 0.001. G Overall postulated mechanism of miR-1 mediated attenuation of SCLC cell growth and metastasis. Low miR-1 and high CXCR4 were associated with SCLC and proposed therapeutic activation or overexpression of miR-1 in SCLC target 3'-UTR of CXCR4, resulting in decreased CXCR4 expression. In addition, miR-1 mediated CXCR4 targeting inhibited FOXM1/RRM2 axis responsible for SCLC growth and metastasis. Schematic created with BioRender.com