| Autor: |
Zhi-Hai, Zheng, He-Yi, You, Yu-Jie, Feng, Zhong-Tao, Zhang |
| Rok vydání: |
2020 |
| Předmět: |
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| DOI: |
10.21203/rs.3.rs-30554/v1 |
| Popis: |
Context: The development of cisplatin resistance is a common cause of cancer recurrence in colorectal cancer (CRC). Long non-coding RNA KCNQ1OT1 has been proven to exert its oncogenic function in multiple cancers. Curcumin is a natural phenolic that could effectively suppress cisplatin resistance in CRC.Objective: To expound the role of KCNQ1OT1 in cisplatin resistance in CRC cells and whether KCNQ1OT1 participates in the reversal effect of curcumin on cisplatin resistance in CRC. Methods: Cell proliferation and apoptosis were evaluated by CCK-8 assay and flow cytometry assay, respectively. The interplay between KCNQ1OT1 and miR-497 was determined using RNA pull-down assay and dual-luciferase reporter gene assay. The combination of B-cell lymphoma 2 (Bcl-2) and miR-497 was confirmed using dual-luciferase reporter gene assay. Results: Compared with CRC cell line HCT8, the cisplatin-resistant CRC cell line HCT8/DDP exhibited a higher KCNQ1OT1 expression. Functionally, the silence of KCNQ1OT1 suppressed proliferation and promoted apoptosis in HCT8/DDP cells. KCNQ1OT1 could act as a sponge of miR-497 and removed the suppressive effect of miR-497 on Bcl-2 expression. Curcumin treatment suppressed proliferation and promote apoptosis in HCT8/DDP cells. While KCNQ1OT1 overexpression removed the effect of curcumin on HCT8/DDP cells via miR-497/ Bcl-2 axis. Finally, the in vivo experiments confirmed that the ectopic expression of KCNQ1OT1 reversed the suppressive effect of curcumin on the growth of cisplatin-resistant CRC cells.Conclusion: KCNQ1OT1 promoted cisplatin resistance in CRC cells via the miR-497/Bcl-2 axis. Administration of curcumin could effectively down-regulate KCNQ1OT1 expression, thus reversing cisplatin resistance in CRC cells. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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