Abstract
The development of cisplatin resistance is a common cause of cancer recurrence in colorectal cancer (CRC). Though many studies have reported the oncogenic function of long non-coding RNA (LncRNA) KCNQ1OT1 in multiple cancers, few studies explored its role in cisplatin resistance of CRC. Curcumin is a natural phenolic compound extracted from turmeric, which can effectively suppress cisplatin resistance in CRC. This study aims 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. 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. Compared with CRC cell line HCT8, the cisplatin-resistant CRC cell line HCT8/DDP exhibited a higher expression level of KCNQ1OT1. Functionally, the silence of KCNQ1OT1 suppressed proliferation and boosted apoptosis in HCT8/DDP cells. Subsequently, we found that KCNQ1OT1 could act as a sponge of miR-497 and remove the suppressive effect of miR-497 on Bcl-2 expression. Curcumin treatment restrained proliferation and facilitated 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 showed that the inhibitory effect of curcumin on the growth of cisplatin-resistant CRC cells was reserved by the ectopic expression of KCNQ1OT1. In conclusion,KCNQ1OT1 aggravated cisplatin resistance in CRC cells via the miR-497/Bcl-2 axis. Administration of curcumin could effectively downregulate KCNQ1OT1 expression, thus reversing cisplatin resistance in CRC cells.
Highlights
Colorectal cancer (CRC) is the most common gastrointestinal malignancy and the third leading cause of cancer-related deaths worldwide [1]
While KCNQ1OT1 overexpression removed the effect of curcumin on HCT8/DDP cells via miR-497/ B-cell lymphoma 2 (Bcl-2) axis
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
Summary
Colorectal cancer (CRC) is the most common gastrointestinal malignancy and the third leading cause of cancer-related deaths worldwide [1]. Despite surgical resection combined with chemotherapeutic agents such as cisplatin achieve good treatment outcomes at the early stages. The development of cisplatin resistance after prolonged treatment is a common cause of cancer recurrence [2]. Clarifying the underlying mechanisms of cisplatin resistance has great significance for the clinical treatment of CRC. B-cell lymphoma 2 (Bcl-2) is a key member of the proto-oncogene Bcl-2 protein family and responsible for the regulation of cell apoptosis [3]. Increasing evidence showed that Bcl-2 contributed to the development of cisplatin resistance in various cancers. In non-small cell lung cancer, the up-regulation of Bcl-2 was associated with the cytoplasmic repressor/activator protein-1-mediated cisplatin resistance [4]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
