Purpose: The long noncoding RNA C1QTNF1 antisense RNA 1 (C1QTNF1-AS1) contributes to hepatocellular carcinoma development. However, its expression and roles in colorectal cancer (CRC) have not been fully explored. Therefore, this study determined the expression and roles of C1QTNF1-AS1 in CRC and elucidated its detailed mechanism of action.
Methods: C1QTNF1-AS1 expression in CRC tissues and cell lines was assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). We used Cell Counting Kit-8, flow cytometry, cell migration and invasion assays, and a xenograft tumor model to test the effects of C1QTNF1-AS1 on CRC malignancy. The associations among C1QTNF1-AS1, microRNA-484 (miR-484), and hexokinase 2 (HK2) were explored using luciferase reporter assay, RNA immunoprecipitation, RT-qPCR, and Western blotting.
Results: C1QTNF1-AS1 was overexpressed in CRC and related to poor prognosis. C1QTNF1-AS1 interference inhibited CRC cell proliferation, migration, and invasion but induced apoptosis. Furthermore, C1QTNF1-AS1 deficiency impaired tumor growth in vivo. Mechanistically, C1QTNF1-AS1 adsorbed miR-484, thereby increasing the expression of its target HK2. Rescue experiments revealed that the effects of C1QTNF1-AS1 deficiency in CRC cells were reversed by inhibiting miR-484 or upregulating HK2.
Conclusion: C1QTNF1-AS1 drives CRC progression by sponging miR-484 and consequently upregulating HK2. The C1QTNF1-AS1/miR-484/HK2 pathway may serve as a diagnostic and therapeutic target for CRC.
Keywords: competitive endogenous RNA; hexokinase 2; therapeutic target.
© 2020 Jin et al.