miR-140-3p is involved in the occurrence and metastasis of gastric cancer by regulating the stability of FAM83B

Abstract

Background Gastric cancer (GC) is a malignant tumor and microRNAs (miRNAs) are closely connected to GC development. The purpose of this study is to investigate the effect of miR-140-3p on the occurrence and metastasis of GC. Methods We detected miR-140-3p expression in GC cells and tissues. The correlation between miR-140-3p and prognosis and clinicopathological features in GC was analyzed. The role of miR-140-3p in GC cell migration, invasion, and proliferation was analyzed. The model of tumor transplantation and metastasis in nude mice was established, and the effect of miR-140-3p on the development and metastasis of GC was assessed. The relation between miR-140-3p and SNHG12 and the relations among HuR, SNHG12, and FAM83B were analyzed. Results miR-140-3p was poorly expressed in GC. GC patients with low miR-140-3p expression had a poor prognosis and unfavorable clinicopathologic features. Overexpression of miR-140-3p inhibited GC cell migration, invasion, and proliferation, and inhibited the development and metastasis of GC. miR-140-3p directly bound to SNHG12 in GC tissues and downregulated SNHG12 expression. SNHG12 overexpression induced HuR nuclear transportation. HuR can bind to FAM83B and up-regulate the mRNA level of FAM83B. Overexpression of SNHG12 or FAM83B reduced the inhibition of overexpression of miR-140-3p on GC. Conclusion miR-140-3p directly bound to SNHG12 in GC and down-regulated the expression of SNHG12, reduced the binding of SNHG12 and HuR, thus inhibiting the nuclear transportation of HuR and the binding of HuR and FAM83B, and reducing the transcription of FAM83B, and finally inhibiting the growth and metastasis of GC.

Exploring the expression and clinical significance of the miR-140-3p-HOXA9 axis in colorectal cancer

“…For instance, low miR-140-3p expression in gastric cancer patients has been associated with poor prognosis and unfavorable clinicopathological features. Overexpression of miR-140-3p inhibits gastric cancer cell migration, invasion, and proliferation (Wang et al 2021 ). Similarly, in bladder cancer, miR-140-3p hinders cancer cell proliferation and invasion by directly targeting FOXQ1 (Wang et al 2020b ).…”

The role of CEMIP in cancers and its transcriptional and post-transcriptional regulation

“…In cutaneous melanoma (CM), diminished miR-140-3p levels correlate with poorer CM survival rates, whereas overexpression of miR-140-3p impedes cell movement ( He et al, 2020 ). Similarly, in gastric cancer, it suppresses the migration and invasion of gastric cancer cells by binding to SNHG12 and suppressing its expression ( Wang et al, 2021 ).…”

Role of exosomal ncRNAs released by M2 macrophages in tumor progression of gastrointestinal cancers

“…In recent studies, the low expression of Exos-miR-140 in GICs was significantly linked to tumor progression, metastasis, and immunosuppression. 109 , 110 Interestingly, upregulation of PD-L1 and decreased CD8 + T cells in the TME of GC might be promoted by reduced expression of miR-140. 111 Overexpression of miR-140 inhibited PD-L1 and Tregs in GC mice model, while it increased the recruitment of CD8 + T cells, leading to inhibition of GC growth.…”