MicroRNA-216b-5p Functions as a Tumor-suppressive RNA by Targeting TPT1 in Pancreatic Cancer Cells

Abstract

MicroRNAs (miRNAs) are increasingly recognized as being involved in pancreatic cancer progression by directly regulating the expression of their targets. In this study, we showed that miR-216b-5p expression was significantly decreased in pancreatic cancer tissues and cell lines. In addition, low miR-216b-5p expression was significantly associated with large tumor size and advanced TNM stage. Meanwhile, both Kaplan-Meier and multivariate survival analysis showed that decreased miR-216b-5p expression was associated with overall survival. miR-216b-5p over-expression repressed pancreatic cancer cell proliferation and induced cell cycle arrest and cell apoptosis in vitro and inhibited tumorigenesis in vivo. The translationally controlled tumor protein (TPT1) was identified as a novel direct target of miR-216b-5p. miR-216b-5p up-regulation suppressed TPT1 expression. Moreover, TPT1 mRNA expression levels were increased in pancreatic cancer tissues, and were inversely correlated with miR-216b-5p expression. TPT1 down-regulation had similar effects as miR-216b-5p up-regulation on pancreatic cancer cell progression. The restoration of TPT1 reversed the effect of miR-216b-5p on pancreatic cancer cell progression. Furthermore, we found that miR-216b-5p up-regulation suppressed Pim-3, Cyclin B1, p-Bad and Bcl-xL protein expression. However, the effect of miR-216b-5p up-regulation was partly reversed by TPT1 up-regulation in vitro. Taken together, our findings suggested that miR-216b-5p functions as a potential tumor suppressor by regulating TPT1 in pancreatic cancer cells, and it may represent a potential therapeutic target for patients with pancreatic cancer.

Dys-regulation of Lnc-SNHG1 and miR-216b-5p Correlate With Chemo-resistance and Indicate Poor Prognosis of Serous Epithelial Ovarian Cancer

“…51.875 ± 5.267 vs 69.373 ± 5.601, P = 0.010) and less DFS (survival interval: 33.978 ± 4.413 vs45.949 ± 4.823 P = 0 .007). By using Spearman's correlation analysis we found signi cantly negative correlations between lnc-SNHG1 and miR-216b-5p (r = -0.424, P = 0.0001) .Interestingly, similar to our study, in the year of 2018, You et al [37] in their study showed decreased expression of miR-216b-5p was signi cantly associated with large tumor size and advanced TNM stage. What's more, low expression level of miR-216b-5p was associated with overall survival by applying both Kaplan-Meier and multivariate survival analysis.…”

Long non-coding RNA TUG1 promotes cell progression in hepatocellular carcinoma via regulating miR-216b-5p/DLX2 axis

“…Many studies have reported that miR-216b-5p was a tumor suppressor with low expression in many cancers [31]. For example, miR-216b-5p as a tumor-inhibiting factor to hinder proliferation by targeting TPT1 in pancreatic cancer cells [32]. A recent study also reported that LINC00152 could modulate the proliferation of cervical cancer (CC) cells through elevating HOXA1 expression level via sponging miR-216b-5p [33].…”

Peer Review #1 of "Identification of key genes and long non-coding RNA associated ceRNA networks in hepatocellular carcinoma (v0.2)"

“…miR-216b-5p is an anti-tumor miRNA found in several cancers. (He et al 2019;Ren et al 2019;Sun et al 2019b;You et al 2017) It is believed that miR-216b-5p inhibits HCV by suppressing host autophagy (Huang et al 2018). Paradoxically, miR-216b-5p represses the expression of UDP-glucuronosyltransferase 2B, a group of enzymes that detoxifies carcinogens by binding to their 3'UTRs.…”