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Multidrug resistance (MDR) has become the major cause of failure chemotherapy for leukemia and high mortality of leukemia. The study aimed to investigate whether the let‐7f mediate the Adriamycin (ADR) resistance of leukemia, and to explore the potential molecular mechanism. Cell proliferation was examined by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide and the soft agar clone formation assay. Flow cytometry was performed to detected cell cycle and apoptosis. The targeted regulationship was analyzed by dual‐luciferase assay. Real‐time polymerase chain reaction and Western blot were used to measure the expressions of let‐7f, ABCC5, ABCC10, cell cycle‐related proteins, and apoptosis‐related proteins. The xenograft mouse model was used to conduct the tumor formation assay in vivo. The results demonstrated that the expression of let‐7f was lower in multidrug‐resistant K562/A02 cell lines compared to that in K562, while ABCC5 and ABCC10 were upregulated. Overexpression of let‐7f in K562/A02 cell lines downregulated the ABCC5 and ABCC10 expression, enhanced cell sensitivity to ADR, promoted cell apoptosis, and inhibited cell proliferation. let‐7f was proved to negatively regulate ABCC5 and ABCC10. Tumor formation assay further determined that let‐7f overexpression increased sensitivity to ADR. Taken together, the let‐7f downregulation induced the ADR resistance of leukemia by upregulating ABCC5 and ABCC10 expression. Our study provided a novel perspective to study the mechanism of MDR and a new target for the reversal of MDR.

Comprehensive analysis on the expression profile and prognostic values of Synaptotagmins (SYTs) family members and their methylation levels in gastric cancer, Bioengineered, 12:1,[3550][3551][3552][3553][3554][3555][3556][3557][3558][3559][3560][3561][3562][3563][3564][3565]

Multiple myeloma (MM) is the second largest hematological tumor with clonal proliferation of malignant plasma cells. Growing reports have revealed that the dysregulation of long non‐coding RNA (lncRNA) is involved in the MM progression. Nevertheless, lncRNA FEZF1 antisense RNA 1 (FEZF1‐AS1) remain not deeply explored. The RNA transcripts and protein level of MM‐associated molecule were measured by quantitative real‐time polymerase chain reaction or western blot assays, respectively. The clinical correlation was analyzed by Pearson analysis. Molecular interactions among lncRNA FEZF1‐AS1, basic leucine zipper and W2 domain 2 (BZW2) and insulin‐like growth factor 2 mRNA‐binding protein 1 (IGF2BP1) were verified by RNA immunoprecipitation and RNA pull‐down assays. The survival of MM cells was detected by cell counting kit‐8 and flow cytometry assays. Xenograft tumor in vivo was performed to assess tumor growth. The RNA transcripts of lncRNA FEZF1‐AS1, BZW2 and IGF2BP1 were upregulated in MM samples compared to those in healthy donors. Knockdown of lncRNA FEZF1‐AS1 could inhibit the proliferation and induce cell apoptosis in vitro and in vivo. Besides, lncRNA FEZF1‐AS1 could maintain the stability of BZW2 mRNA by interacting IGF2BP1. Moreover, BZW2 silence also downregulated the proliferation but enhanced apoptosis of MM cells, while BZW2 overexpression had an opposite role, which dramatically reversed the regulatory roles of lncRNA FEZF1‐AS1. Altogether, lncRNA FEZF1‐AS1 facilitated MM development by regulating IGF2BP1/BZW2 signaling, suggesting that lncRNA FEZF1‐AS1 might be a candidate for MM treatment.

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