LncRNA GAPLINC Promotes Renal Cell Cancer Tumorigenesis by Targeting the miR-135b-5p/CSF1 Axis

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.

A Novel Prognostic Signature Associated With the Tumor Microenvironment in Kidney Renal Clear Cell Carcinoma

“…CSF1 acts as a tumour-promoting cytokine by recruiting macrophages to the tumour area, which in turn leads to the release of various tumour-promoting growth factors in the microenvironment (32). In vitro and in vivo studies have confirmed that CSF1 promotes proliferation and reduces apoptosis in renal cell carcinoma (33). TUBB2B alterations can lead to increased incidence of kidney disease and KIRC (34).…”

Identification of a ferroptosis-related long noncoding RNA signature with a prognostic value in adrenocortical carcinoma

“…Similarly, LINC00460 in head and neck squamous cell carcinoma facilitates peroxiredoxin-1 entry into the nucleus, thereby promoting cell proliferation and metastasis ( Jiang et al, 2019 ). Knockdown of lncRNA GAPLINC repressed the tumor growth in renal cell cancer, while overexpression of GAPLINC facilitated tumorigenesis via the miR-135b-5p/CSF1 axis, indicating poor survival ( Wang et al, 2021c ). On the other hand, Yang and colleagues revealed that lncRNA MYOSLID played a critical role in the progression of osteosarcoma through the miR-1286/RAB13 axis ( Yang et al, 2019a ).…”

Preliminary study on the role of the C5orf46 gene in renal cancer

“…After 24 hours of incubation, the cells in the lower chamber were collected, fixed and stained. Other cell function assays, such as plate colony formation [11] and Cell Counting Kit-8 (CCK-8) assays [12] and flow cytometry analyses of the cell cycle [13] and apoptosis [14] , were conducted as previously described.…”