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.
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
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
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.