The protective role of all-transretinoic acid (ATRA) against colorectal cancer development is achieved via increasing miR-3666 expression and decreasing E2F7 expression

Abstract

OBJECTIVE: Colorectal cancer (CRC) is one of the most common malignancies with high morbidity and mortality rates worldwide. This study aimed to investigate whether miR-3666 was involved in inhibitory effects of all-transretinoic acid (ATRA) on the development of colorectal cancer (CRC).

MATERIAL AND METHODS: Surgical specimens of CRC tissues and adjacent non-tumor mucosa were collected for determining miR-3666 expression. Human CRC HCT116 cells were treated with different doses of ATRA (10, 20, 40, and 60 μM, respectively) and/or transfected with miR-3666 mimic, miR-3666 inhibitor, E2F7 siRNAs or their controls, respectively. After different treatments, cell viability, apoptosis, migration and invasion were detected. The regulatory relationship between miR-3666 and E2F7 was investigated. Furthermore, the association between MAPK/ERK pathway and ATRA or miR-3666/E2F7 was explored.

RESULTS: The miR-3666 was lowly expressed in CRC tissues, while E2F7 was highly expressed. ATRA decreased HCT116 cell viability, migration, and invasion, and induced apoptosis, indicating that ATRA inhibited the malignant behaviors of HCT116 cells. Moreover, ATRA increased miR-3666 expression, and effects of ATRA on the malignant behaviors of HCT116 cells were achieved by positive regulating miR-3666 expression. Furthermore, E2F7 was a target gene of miR-3666, and knockdown of E2F7 reversed the combined effects of ATRA and miR-3666 inhibitor on the malignant behaviors of HCT116 cells. Besides, ATRA inhibited the activation of MAPK/ERK signaling pathway, which was reversed by inhibition of miR-3666.

CONCLUSIONS: Our results reveal that ATRA protects against CRC development possible via increasing miR-3666 expression and decreasing E2F7 expression. MiR-3666/E2F7 may play a key role in regulating the inhibitory effects of ATRA on HCT116 cells via suppressing the activation of MAPK/ERK signaling pathway.

 

About this publication.

See also:

- Official Web Site: The Di Bella Method;

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- The Di Bella Method (A Fixed Part - All-Trans Retinoic Acid, Analogues and/or Derivatives - Approximately 60mg per day orally: 40mg per day Beta-Carotene/β-Carotene, 10mg per day ATRA and 10mg per day Axerophthol palmitate);

- All-Trans-Retinoic Acid (ATRA - analogues and/or derivatives) - In vitro, review and in vivo publications;

- Solution of retinoids in vitamin E in the Di Bella Method biological multitherapy;

- The Di Bella Method (A Fixed Part - Alpha tocopheryl acetate/Vitamin E, approximately 20 grams per day orally);

- Cancer and Vitamin E (analogues and/or derivatives) and cancer - In vitro, review and in vivo publications;

- The Di Bella Method (A Fixed Part - Cyclophosphamide 50mg tablets and/or Hydroxyurea 500mg tablets, one or two per day);

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