Aligned submicron fibers have played an essential role in inducing stem cell proliferation and differentiation. In this study, it is aimed to identify the differential causes of stem cell proliferation and differentiation between bone marrow mesenchymal stem cells (BMSCs) on aligned-random fibers with different elastic modulus, and to change the differential levels through a regulatory mechanism mediated by B-cell lymphoma 6 protein(BCL-6) and miRNA-126-5p(miR-126-5p). The results showed that phosphatidylinositol(4,5)bisphosphate alterations are found in the aligned fibers compared with the random fibers, which has a regular and oriented structure, excellent cytocompatibility, regular cytoskeleton, and high differentiation potential. The same trend is actual for the aligned fibers with a lower elastic modulus. The level of proliferative differentiation genes in cells is altered by BCL-6 and miR-126-5p mediated regulatory mechanisms to make the cell distribution nearly consistent with the cell state on low elastic modulus aligned fibers. This work demonstrates the reason for the difference of cells between the two kinds of fibers and on fibers with different elastic modulus. These findings provide more insights for understanding the gene-level regulation of cell growth in tissue engineering.