Figure 2.

The schematic diagram of the effects of 5-FU on G1 and G2 phase cell cycle arrest in tumor cells through regulation by various non-coding RNAs. 5-fluorouracil has been highly applied for chemotherapy of gastrointestinal cancers and is known to affect the cell cycle and trigger apoptotic death of cancer cells. Non-coding RNAs have an important role in regulating cell cycle mechanisms via modulating the effects of 5-FU on the expression of G1/S and G2/M-related cell cycle regulators in tumor cells. LncRNA HOTAIR via downregulating the expression level of miR-218 and promoting the activation of NF-κB/TS signaling cascade could induce upregulation of the cell cycle transcription factor E2F-1, and thereby contributing to 5-FU Resistance and elevating enhanced colorectal cancer cell carcinogenesis (124). Besides, miR-381 via downregulation of the expression level of WEE1 and upregulation of the activity of Cdc2 results in alteration in cell cycle regulation which could potentiate the anti-tumor efficacies of 5-FU and abrogate G2/M cell cycle arrest in renal cancer cells (118). Additionally, miR-195 via directly targeting checkpoint kinase 1 (CHK1) and G2 checkpoint kinase WEE1 could desensitize colorectal cancer cells to 5-FU. This result demonstrates that miR-195 has a potential role in promoting the cell cycle via elevating G2/M transition after exposure to 5-FU (62).