LAUSR

Abstract The molecular mechanisms underlying the anti‐neoplastic properties of metformin, a first‐line drug for type 2 diabetes, remain elusive. To explore the novel anti‐neoplastic mechanisms of metformin, the transwell chamber and wound‐healing assays were used to evaluate its effects on the migration and invasion of human cervical cancer cells. Real‐time PCR and Western blotting were used to measure the gene and protein expression, respectively, of microRNA (miRNA) miR‐142‐3p, long non‐coding RNA (lncRNA) metastasis‐associated lung adenocarcinoma transcript‐1 (MALAT1), and high‐mobility group AT‐hook 2 (HMGA2). The dual‐luciferase reporter assay system was used to examine the direct interaction between miR‐142‐3p and lncRNA MALAT1 and HMGA2. Immunofluorescence was used to detect the protein expression of HMGA2. In addition, tumor xenografts in a nude mouse model were developed to evaluate the anti‐tumor efficacy of metformin. We found that metformin could suppress cervical cancer migration and invasion. During the process of tumor metastasis, miR‐142‐3p was significantly upregulated, whereas lncRNA MATAL1 and HMGA2 were suppressed by metformin. The binding site that allow the direct interaction between miR‐142‐3p and MALAT1 were located in the 3′ untranslated region (3′ UTR) of lncRNA MATAL1 and HMGA2 at base pairs (bp) 4452–5255, while that between miR‐142‐3p and HMGA2 was located at bp 1562–2521 of HMGA2. Metformin markedly inhibited the growth and angiogenesis of SiHa xenografts in nude mice. In conclusion, this study provides evidence that metformin can prevent the MALAT1/miR‐142‐3p sponge from developing anti‐neoplastic properties in human cervical cancer cells and cervical cancer cell xenografts in nude mice. Thus, our findings demonstrate the novel anti‐tumor effects of metformin in cervical cancer.