Rotundic Acid Regulates the Effects of Let-7f-5p on Caco2 Cell Proliferation

Author(s):

Yuan Feng, Xinran Liu, Yueqing Han, Mantian Chen, Lin Zhang, Yuling Hu, Liya Chen, Gang Chen* and Ning Li*   Pages 902 - 909 ( 8 )

Abstract:

<P>Background & Objective: Nowadays, the interaction between natural products and microRNAs provides a promising field for exploring the chemopreventive agents for various cancers. As a member of microRNAs, the expression of let-7f-5p is universally downregulated in Colorectal Cancer (CRC). The present study aimed to uncover the function of let-7f-5p in the proliferation of human colon cancer cell line Caco2 and explored chemopreventive agents from natural resources that can prevent the development of CRC. </P><P> Methods: Herein, Caco2 cells were transfected with let-7f-5p mimic and inhibitor to manipulate let-7f-5p levels, and the expression of let-7f-5p was performed by RT-qPCR. Next, we determined how let-7f-5p regulates Caco2 cell proliferation by using MTT, wound-healing, cell cycle, and colony formation assays. Besides, to further understand the effect of let-7f-5p, we evaluated the protein level of AMER3 and SLC9A9 by using western blotting assays. </P><P> Results: The results showed a suppressive function of let-7f-5p on Caco2 cell proliferation and then put forward a triterpenoid (Rotundic Acid, RA) which significant antagonized the effect of cell proliferation, restitution after wounding, and colony formation caused by let-7f-5p. Moreover, the western blot results further indicated that the inhibitory effect of RA might be due to its suppressive role in let-7f-5p-targeted AMER3 and SLC9A9 regulation. </P><P> Conclusion: Our validation study results confirmed that let-7f-5p was a potent tumor suppressor gene of Caco2 cell proliferation, and RA showed as a regulator of the effect of let-7f-5p on cell proliferation and then could be a potential chemopreventive agent for CRC treatment.</P>

Keywords:

Caco2 cells, colorectal cancer, let-7f-5p, rotundic acid, proliferation, AMER3, SLC9A9.

Affiliation:

School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University; Key Laboratory of Computational Chemistry- Based Natural Antitumor Drug Research & Development, Liaoning Province, Wenhua Road 103, Shenyang 110016, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University; Key Laboratory of Computational Chemistry- Based Natural Antitumor Drug Research & Development, Liaoning Province, Wenhua Road 103, Shenyang 110016, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University; Key Laboratory of Computational Chemistry- Based Natural Antitumor Drug Research & Development, Liaoning Province, Wenhua Road 103, Shenyang 110016, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University; Key Laboratory of Computational Chemistry- Based Natural Antitumor Drug Research & Development, Liaoning Province, Wenhua Road 103, Shenyang 110016, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University; Key Laboratory of Computational Chemistry- Based Natural Antitumor Drug Research & Development, Liaoning Province, Wenhua Road 103, Shenyang 110016, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University; Key Laboratory of Computational Chemistry- Based Natural Antitumor Drug Research & Development, Liaoning Province, Wenhua Road 103, Shenyang 110016, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University; Key Laboratory of Computational Chemistry- Based Natural Antitumor Drug Research & Development, Liaoning Province, Wenhua Road 103, Shenyang 110016, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University; Key Laboratory of Computational Chemistry- Based Natural Antitumor Drug Research & Development, Liaoning Province, Wenhua Road 103, Shenyang 110016, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University; Key Laboratory of Computational Chemistry- Based Natural Antitumor Drug Research & Development, Liaoning Province, Wenhua Road 103, Shenyang 110016

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