Study on the mechanism of let-7a-5p in regulating the proliferation in cervical cancer cells

Abstract

Purpose: To explore the regulatory effect of let-7a-5p/TGFBR1/Smad3 on the proliferation activity of cervical cancer cells.

Methods: The difference in let-7a-5p expression between normal people and patients with cervical cancer was detected by miREIA assay. The differences of let-7a-5p expression between cervical cancer cell line C33a and adjacent normal epithelial cell line HUCEC were determined by qRT-PCR.

Results: miREIA result showed that let-7a-5p concentrations were 178.5 ± 24.3 μg/L in healthy individuals and 106.1 ± 14.8 μg/L in cervical cancer patients (P = 0.0002). qRT-PCR showed that let-7a-5p in cervical cancer tissue (0.57 ± 0.03) was lower than that in adjacent normal tissue (0.84 ± 0.04, P = 0.0107). Compared with normal cervical epithelial cells (HUCEC), the expression of let-7a-5p was lower in cervical cancer cells (C33a, Hela, P = 0.0001). The results of CCK-8 and EDU detection showed that activation of let-7a-5p inhibited the proliferation of C33a (P = 0.00130, P << 0.0001) and Hela (P = 0.00254, P = 0.0066) cells. According to the analysis using Starbase V2.0 online database, let-7a-5p could target TGFβR1 in cervical cancer cell lines, and the let-7a-5p mimic reduces the mRNA expression level of TGFβR1 in cervical cancer cell C33a (P = 0.0067). Western blot results showed that TGFBR1 expression significantly decreased in cervical cancer cells after let-7a-5p mimic treatment (P = 0.0048) and significantly increased after let-7a-5p mimic inhibitor treatment (P = 0.0003).

Conclusions: let-7a-5p represents the independent novel anti-oncogenes in cervical cancer, which can regulate TGF-β1/TGFBR1/pSmad3 cell pathway and interfere with the proliferation of cervical cancer cells. Therefore, let-7a-5p can serve as a novel potential therapeutic target for the treatment of cervical cancer.

Keywords: Cervical cancer; Let-7a-5p; Smad3 signal; TGF-β1.