miR-20b reduces 5-FU resistance by suppressing the ADAM9/EGFR signaling pathway in colon cancer

Abstract

Chemoresistance is a major obstacle to cancer therapy including that of colon cancer (CC). Although the dysregulation of many miRNAs has been implicated in 5-fluorouracil (5-FU) resistance in CC cells, the specific role of miR-20b in chemoresistance has not been documented. In the present study, we first determined the expression of miR-20b by RT-PCR and the levels of a disintegrin and metalloprotease 9 (ADAM9) and epidermal growth factor receptor (EGFR) by western blotting in CC and adjacent non-cancerous tissues from 5-FU-sensitive or -resistant CC patients. Subsequently, 5-FU-sensitive (HCT116) and -resistant (HCT116-R) cells were obtained, and the levels of miR-20b, ADAM9 and EGFR were detected. Meanwhile, the 5-FU resistance of the cells was examined by assessing cell viability (by MTT assay) and apoptosis (by flow cytometry). After transfection of miR-20b into HCT116-R cells, drug resistance was reexamined. We then confirmed the relationship between miR-20b and ADAM9 by luciferase reporter assay. Finally, 5-FU resistance in HCT116 and HCT116-R cells was compared after transfection with miR-20b. Our results showed that miR-20b was expressed at lower levels in the 5-FU-resistant tissues and cells than in the 5-FU-sensitive tissues and cells. The opposite was the case for expression of ADAM9 and EGFR. In addition, we demonstrated that ADAM9 is a direct target of miR-20b and that miR-20b decreased the 5-FU resistance of HCT116-R cells. Our findings suggest that miR-20b reduces 5-FU resistance to induce apoptosis in vitro by suppressing ADAM9/EGFR in CC cells.

The Network of Non-coding RNAs in Cancer Drug Resistance

“…In particular miR-587 (369), miR-195 (375), miR-149 (376), miR-203 (377), miR-129 (378), and miR-218 (209) are involved in 5-FU response. While miR-20b (379) and miR-519c (380) influence 5-FU and Irinotecan (only miR-519c) resistance in CRC. Another interesting miRNA is miR-302a, belonging to the miR-302-367 cluster, which includes miR-302b, miR-302c, miR-302a, miR-302d, and miR-367.…”

Long non‐coding RNA POU6F2‐AS2 promotes cell proliferation and drug resistance in colon cancer by regulating miR‐377/BRD4

“…5‐FU was the most widely used drug in the treatment of colon cancer, and resistance to 5‐Fu was the main reason for failure of chemotherapy . Though various miRNAs were demonstrated to regulate 5‐FU resistance in colon cancer cells, lncRNAs and related mechanisms were rarely researched. In this paper, we focused on the inhibition of lncRNA POU6F2‐AS2 for 5‐FU resistance and confirmed it in vivo.…”

The role of microRNAs in 5‐FU resistance of colorectal cancer: Possible mechanisms

“…MiR‐20b expression is lower in the 5‐FU‐resistant tissues and cells than in the 5‐FU‐sensitive tissues and cells. The opposite is the case for expression of ADAM9 and EGFR (Fu et al, ; Figure ).…”