LncRNA MT1JP Suppresses Gastric Cancer Cell Proliferation and Migration Through MT1JP/MiR-214-3p/RUNX3 Axis

Abstract

Background/Aims: Emerging evidence points towards an important role of long noncoding RNAs (lncRNAs) in the tumorigenesis and progression of gastric cancer (GC). MT1JP has recently been reported to be differentially expressed and act as a tumor suppressor in different tumors, with its mechanisms not fully understood in GC. Methods: RT-qPCR was used to detect the expression of MT1JP, miR-214-3p and RUNX3 in tumor tissues and cell lines of GC. The CCK-8 assay, colony formation, Transwell assay and wound healing assay were used to evaluate the proliferation, invasion and migration of GC cells, respectively. Bioinformatics analysis and luciferase reporter assay were performed to disclose the interaction between MT1JP, miR-214-3p and RUNX3. Western blot and immunofluorescence were applied to assess the downstream signaling of RUNX3. Results: MT1JP was found downregulated in GC tissues and cells. Low expression of MT1JP was significantly correlated with advanced TNM stage and lymphatic metastasis. The expression of plasma MT1JP was also found decreased in GC patients compared to healthy controls, with an area under the ROC curve (AUC) of 0.649 for diagnosis of GC. Gain-and loss-of-function of MT1JP revealed that MT1JP functioned as a ceRNA for miR-214-3p to facilitate RUNX3 expression and then upregulated p21 and Bim levels suppressing GC cell proliferation, invasion and migration, and promoting apoptosis. Furthermore, MT1JP overexpression suppressed tumor growth and inhibited the expression of miR-214-3p and proliferation antigen Ki-67, but increased the expression of RUNX3, p21 and Bim in vivo. Conclusions: Our results suggest a potential ceRNA regulatory network involving MT1JP regulates RUNX3 expression by competitively binding endogenous miR-214-3p in tumorigenesis and progression of GC. This mechanism may contribute to a better understanding of GC pathogenesis and provide potential therapeutic strategy for GC.

Retracted: LncRNA MT1JP functions as a tumor suppressor via regulating miR‐214‐3p expression in bladder cancer

“…Increasing studies revealed that lncRNAs play an effect on several cellular functions such as cell growth, development, migration, differentiation, metabolism, and many other cell biological processes (Gao, Lv, Li, Han, & Zhang, 2017;Iancu et al, 2017;G. Wang, Pan, Zhang, Wei, & Wang, suppressor gene in several tumors (L. H. Liu, Yue, et al, 2016;Xu et al, 2018;Yang et al, 2017;C. L. Zhu, Ma, Li, Zhang, & Da, 2018).…”

Long non‐coding RNA LINC01225 promotes proliferation, invasion and migration of gastric cancer via Wnt/β‐catenin signalling pathway

“…The stability of circulating lncRNA has been well documented in previous studies. 10,11 Herein, we found that the expression levels of plasma LINC01225 were significantly higher in GC patients than those in healthy controls ( Figure 1H). Up-regulation of plasma LINC01225 was significantly associated with advanced TNM stage and positive lymphatic metastasis, respectively ( Figure 1J).…”

“…9 Our previous study showed that lncRNA MT1JP suppressed GC cell proliferation and migration by modulating miR-214-3p/RUNX3 axis. 10 Given that the current understanding on GC-associated lncRNAs may represent only the tip of iceberg, additional wok is still needed to further clarify the functional roles of many other lncRNAs in GC development.…”

Long noncoding RNA DGCR5 suppresses gastric cancer progression by acting as a competing endogenous RNA of PTEN and BTG1

“…According to the ceRNA theory, lncRNAs, mRNAs, and pseudogenes can communicate with each other by competing for common MRE. We have previously shown that lncRNA MT1JP suppressed GC cell proliferation and migration by sponging miR‐214‐3p (Xu et al, ). The potential role of DGCR5 as a ceRNA has already been documented in pancreatic ductal adenocarcinoma and lung cancer (Chen et al, ; Dong et al, ; Luo et al, ; R. Wang et al, ; Yong et al, ).…”

“…The procedure was carried out as previously described (Xu et al, ). Briefly, total RNAs were extracted using TRIzol Reagent (Sangon Biotech, Shanghai, China).…”