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5-Fluorouracil (5-FU) resistance has been long considered as an obstacle to the efficacy of chemotherapy in colorectal cancer (CRC). In this study, we demonstrated the role of miR-20b-5p-regulated syndecan-2 (SDC2) in 5-FU resistance of CRC cells. 5-FU-resistant SW480 CRC cells were established by treatment of SW480 cells with stepwise increase of 5-FU concentration. The results showed that SDC2 was expressed significantly higher in SW480/5-FU cells than in SW480/WT cells as revealed by quantitative real-time polymerase chain reaction and western blot analysis. MTT assay and BrdU assay showed that SDC2 overexpression led to increased cell survival rate, while SDC2 knockdown reversed the drug resistance of SW480/5-FU cells. Wound healing and transwell invasion assays revealed that knockdown of SDC2 inhibited the migratory and invasive ability of SW480/5-FU cells. Moreover, animal experiments indicated that si-SDC2 plays a suppressive role in tumor growth in vivo. We also confirmed that miR-20b-5p interacted with SDC2, which reversed the effect of SDC2 in SW480/5-FU cells via the c-Jun N-terminal kinase (JNK)/extracellular regulated protein kinases (ERK) signaling pathway. These findings showed that JNK/ERK signaling pathway is involved in miR-20b-5p/SDC2 axis-mediated 5-FU resistance in SW480/5-FU cells, indicating that the miR-20b-5p/SDC2 axis is a potential target for reversing 5-FU resistance in CRC., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Sorafenib (SOR) resistance is still a significant challenge for the effective treatment of hepatocellular carcinoma (HCC). The mechanism of sorafenib resistance remains unclear. Several microRNAs (miRNAs) have been identified as playing a role in impairing the sensitivity of tumor cells to treatment. We examined the mechanism behind the role of miR-92b in mediating sorafenib resistance in HCC cells. We detected that miR-92b expression was significantly upregulated in SOR-resistant HepG2/SOR cells compared to parental HepG2/WT cells. After transfection with miR-92b inhibitor, the proliferation of HepG2/SOR cells was remarkably weakened and rates of apoptosis significantly increased. PTEN was considered to be a functional target of miR-92b according to a luciferase reporter assay. Knockdown of PTEN significantly impaired the ability of miR-92b inhibitor on increasing sorafenib sensitivity of HepG2/SOR cells. Furthermore, we confirmed by western blotting and immunofluorescence that miR-92b can mediate sorafenib resistance by activating the PI3K/AKT/mTOR pathway in HCC cells by directly targeting PTEN. These findings further validate the mechanism of miR-92b in SOR resistance in HCC treatment.

MicroRNAs (miRNAs) are thought to be involved in the development of cisplatin (DDP) resistance in gastric cancer (GC). Using RNA sequencing analysis (RNA-seq), we found that miR-95-3p is associated with DDP resistance in GC. We discovered that miR-95-3p is highly expressed in DDP-resistant GC tissues and cell lines (SGC7901/DDP and AGS/DDP). Furthermore, results from the BrdU and MTT assays indicated that miR-95-3p promotes GC cell proliferation. Additionally, data from transwell chamber assay, wound healing test and in vivo experiments illustrated that miR-95-3p can effectively promote invasion, migration and tumorigenic capacity, respectively, of DDP-resistant GC cells. Subsequently, results from dual luciferase assay and qRT-PCR collectively indicated that EMP1 is a target of miR-95-3p with inhibitory function through suppression of the EMT process and drug-resistance proteins. Furthermore, PI3K/AKT was identified as a downstream pathway of miR-95-3p, which promotes DDP resistance in GC. In summary, miR-95-3p helped develop DDP-resistance through down-regulation of EMP1 and increasing phosphorylation of the PI3K/Akt pathway in GC.