MicroRNA-381 inhibits cell proliferation and invasion in endometrial carcinoma by targeting the IGF-1R

Abstract

Endometrial carcinoma (EC) is the sixth most common type of malignant tumor occurring in females. MicroRNAs (miRNAs) serve as oncogenes or tumor suppressors in human cancer and play important roles in tumorigenesis, and tumor development by regulating various processes. Thus, further investigation into miRNAs involved in EC formation and progression may aid in developing effective therapeutic strategies for patients with this disease. miRNA‑381 (miR‑381) is aberrantly expressed in multiple types of human cancer. However, the expression pattern, biological roles and underlying mechanisms of miR‑381 in EC are poorly understood. In the present study, the results showed that miR‑381 was downregulated in EC tissues and cell lines. Decreased miR‑381 expression correlated with the International Federation of Gynecology and Obstetrics stage, lymph nodes metastasis and myometrial invasion of EC. The ectopic expression of miR‑381 significantly inhibited the proliferation and invasion of EC cells. Through a series of experiments, the insulin‑like growth factor receptor 1 (IGF‑1R) was identified as a novel direct target of miR‑381 in EC. Furthermore, IGF‑1R was highly expressed in EC tissues and inversely correlated with miR‑381 levels. IGF‑1R overexpression partially abrogated the tumor‑suppressive effects of miR‑381 on the proliferation and invasion of EC cells. miR‑381 targeted IGF‑1R to inactivate the protein kinase B (AKT) and extracellular signal‑regulated kinase (ERK) signaling pathways in EC. These results suggest that miR‑381 acts as a tumor suppressor in EC by directly targeting IGF‑1R, and indirectly regulating the AKT and ERK signaling pathways. Thus, miR‑381 should be investigated as a prognostic biomarker and novel therapeutic target for the treatment of patients with EC.

Non-Coding RNAs in Endometrial Physiopathology

“…Therefore, if it is over-expressed, as in most malignant tissues, it plays an anti-apoptotic role, promoting cancer cell survival and tumour metastasis [ 67 , 68 ]. Recent studies demonstrated that IGF1R was highly expressed in EC tissues and it was inversely correlated with miR-381 levels [ 69 ].…”

Bioinformatics Identification of the Expression and Clinical Significance of E2F Family in Endometrial Cancer

“…Our previous study demonstrated that MIR-302C could suppress EMT and induce apoptosis in EC ( Li et al, 2018 ). In the same cancer type, MIR-381 could suppress proliferation and invasion of tumor cells ( Tu et al, 2018 ). Therefore, regulation of these miRNAs by E2F exacerbate tumorigenesis and progression of ECs.…”

Prognostic value of microRNAs in lung cancer: A systematic review and meta‑analysis

“…miR-26b was shown to function as a critical regulator of tumor progression and carcinogenesis because it acts as either a tumor suppressor or an oncogene in various cancers (29). miR-381 targeted IGF-1R to deactivate the protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) signaling pathways (47). Overexpression of miR-146α significantly enhanced cell apoptosis, inhibiting cell viability and motility in vitro and in vivo and miR-146α could specially degrade the mRNA of cyclin J in the development of acquired drug resistance to DDP-based chemotherapy in NSCLC cells (48).…”