Abstract

BackgroundLong noncoding RNAs (lncRNAs) are closely related to the occurrence and development of cancer. Gastric adenocarcinoma-associated, positive CD44 regulator, long intergenic noncoding RNA (GAPLINC) is a recently identified lncRNA that can actively participate in the tumorigenesis of various cancers. Here, we investigated the functional roles and mechanism of GAPLINC in renal cell carcinoma (RCC) development.MethodsDifferentially expressed lncRNAs between RCC tissues and normal kidney tissues were detected by using a microarray technique. RNA sequencing was applied to explore the mRNA expression profile changes after GAPLINC silencing. After gain- and loss-of-function approaches were implemented, the effect of GAPLINC on RCC in vitro and in vivo was assessed by cell proliferation and migration assays. Moreover, rescue experiments and luciferase reporter assays were used to study the interactions between GAPLINC, miR-135b-5p and CSF1.ResultsGAPLINC was significantly upregulated in RCC tissues and cell lines and was associated with a poor prognosis in RCC patients. Knockdown of GAPLINC repressed RCC growth in vitro and in vivo, while overexpression of GAPLINC exhibited the opposite effect. Mechanistically, we found that GAPLINC upregulates oncogene CSF1 expression by acting as a sponge of miR-135b-5p.ConclusionTaken together, our results suggest that GAPLINC is a novel prognostic marker and molecular therapeutic target for RCC.

Highlights

  • Long noncoding RNAs are closely related to the occurrence and development of cancer

  • The Long noncoding RNAs (lncRNAs) expression of GAPLINC in 539 renal cell carcinoma (RCC) tumor tissues and 72 nontumor tissues was analyzed based on the TCGA database (Figure 1E)

  • Drugs targeting the vascular endothelial growth factor (VEGF) pathway and drugs inhibiting the mammalian target of rapamycin protein have been used in the treatment of metastatic renal cell carcinoma (mRCC)

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Summary

Introduction

Long noncoding RNAs (lncRNAs) are closely related to the occurrence and development of cancer. Gastric adenocarcinoma-associated, positive CD44 regulator, long intergenic noncoding RNA (GAPLINC) is a recently identified lncRNA that can actively participate in the tumorigenesis of various cancers. We investigated the functional roles and mechanism of GAPLINC in renal cell carcinoma (RCC) development. Despite the development and wide application of drugs with different mechanisms of action, GAPLINC in Renal Cancer metastatic renal cell carcinoma (mRCC) is still a highly lethal malignant tumor that presents great challenges [4]. MiRNAs are post-transcriptional regulators of gene expression and promising candidates for biomarker development. They play pivotal roles in a wide variety of biological processes, including cell proliferation, survival, differentiation, and tumorigenesis [8]. The role of ceRNAs in regulating tumor cell proliferation, migration, apoptosis, cell cycle, metastasis, angiogenesis and metabolism has been reported by many laboratories [12]

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