Published online Apr 15, 2020. doi: 10.4251/wjgo.v12.i4.394
Peer-review started: December 21, 2019
First decision: January 19, 2020
Revised: February 4, 2020
Accepted: March 22, 2020
Article in press: March 22, 2020
Published online: April 15, 2020
Gastric cancer (GC) is one of the most aggressive malignancies, with a high incidence and poor prognosis worldwide. Recently, accumulating evidence has illustrated that long noncoding RNAs (lncRNAs) play pivotal roles in many cancers. It has been reported that LINC00511 contributes to tumorigenesis in various diseases. However, the role of LINC00511 in GC cell growth remains mostly unknown.
To determine whether the lncRNA LINC00511 exerted its carcinogenic function in GC via the miR-124-3p/PDK4 axis.
Cell culture and transfection, RNA extraction and quantitative real-time PCR, CCK-8 assay, Colony formation assay, Luciferase reporter assay, RIP assay, RNA pull-down assay, and Western blot analysis were used to show expression and mechanisms of LINC00511 in GC progression and apoptosis. Rescue assays were performed to verify the relationships among LINC00511, miR-124-3p and PDK4 further.
The expression of LINC00511 was remarkably upregulated in GC cells compared to that in corresponding normal cell lines. Compared to the controls, cell proliferation was inhibited, and cell apoptosis was increased upon LINC00511 knockdown, demonstrating that LINC00511 influenced GC cell growth. An exploration of the molecular mechanism revealed that LINC00511 functioned as a molecular sponge of miR-124-3p and that PDK4 was a downstream target of miR-124-3p in GC. Rescue assays showed that the overexpression of PDK4 could partly restore the inhibitory function of si-LINC00511 in GC.
These data demonstrate that LINC00511 promotes gastric cancer cell growth by acting as a ceRNA to regulate the miR-124-3p/PDK4 axis, which may be a promising therapeutic target for GC.
Core tip: In this study, we aimed to determine whether the long noncoding RNAs LINC00511 exerted its carcinogenic function in gastric cancer (GC) via the miR-124-3p/PDK4 axis. First, we investigated the expression level of LINC00511 in GC cell lines, and we then examined the biological function of LINC00511 with functional assays. Next, we predicted and confirmed the interaction between LINC00511 and miR-124-3p. Furthermore, we further found that PDK4 was a downstream target of miR-124-3p. Finally, we concluded that LINC00511 plays an oncogenic role in GC by sponging miR-124-3p and targeting PDK4, indicating that LINC00511 may be a new molecular biomarker for GC.