Long noncoding RNA LINC00261 suppresses prostate cancer tumorigenesis through upregulation of GATA6-mediated DKK3

Abstract

Background Prostate cancer is one of the leading causes of cancer death in males. Recent studies have reported aberrant expression of lncRNAs in prostate cancer. This study explores the role of LINC00261 in prostate cancer progression. Methods The differentially expressed genes, transcription factors, and lncRNAs related to prostate cancer were predicted by bioinformatics analysis. Prostate cancer tissue samples and cell lines were collected for the determination of the expression of LINC00261 by reverse transcription quantitative polymerase chain reaction. The binding capacity of LINC00261 to the transcription factor GATA6 was detected by RIP, and GATA6 binding to the DKK3 promoter region was assessed by ChIP. In addition, luciferase reporter system was used to verify whether LINC00261 was present at the DKK3 promoter. After gain- and loss-of function approaches, the effect of LINC00261 on prostate cancer in vitro and in vivo was assessed by the determination of cell proliferation, invasion and migration as well as angiogenesis. Results LINC00261, GATA6, and DKK3 were poorly expressed in prostate cancer. LINC00261 could inhibit transcriptional expression of DKK3 by recruiting GATA6. Overexpression of LINC00261 inhibited prostate cancer cells proliferation, migration, and invasion as well as angiogenesis, which could be reversed by silencing DKK3. Furthermore, LINC00261 could also suppress the tumorigenicity of cancer cells in vivo. Conclusions Our study demonstrates the inhibitory role of LINC00261 in prostate cancer progression, providing a novel biomarker for early detection of prostate cancer.

LINC00261 Suppresses Cisplatin Resistance of Esophageal Squamous Cell Carcinoma Through miR-545-3p/MT1M Axis

“…For example, overexpression of FOXD2-AS1 enhanced DDPresistance in ESCC tissues and cells, and silencing FOXD2-AS1 improved DDP-resistance in ESCC (Liu H. et al, 2020). LINC00261 acts as a tumor suppressor gene in many cancers, LINC00261 suppresses the growth and metastasis of liver cancer, prostate cancer, and pancreatic cancer (Guo et al, 2020;Li Y. et al, 2020;. It has been stated in the results that LINC00261 is the candidate gene screened in our previous experiments.…”

LINC00261: a burgeoning long noncoding RNA related to cancer

“…Similarly, for esophageal cancer, the anti-tumor influence of LINC00261 was determined using 5-fluorouracil (5-FU) to detect increased drug sensitivity in human esophageal cancer cells [87]. Other studies have also demonstrated an inhibitory effect of LINC00261 expression in prostate cancer, choriocarcinoma, and cholangiocarcinoma [38,88,89].…”

“…In prostate cancer, the overexpression of LINC00261 was shown to inhibit the transcription of dickkopf-related protein 3 (DKK3) by recruiting GATA binding protein 6 (GATA6), resulting in the inhibition of tumor angiogenesis; this action was reversed by silencing DKK3. Interestingly, in prostate cancer cells, DKK3 expression induced cellular quiescence through the activation of p38 MAPK signaling pathway [ 88 ]. These findings demonstrate that LINC00261 expression may suppress prostate cancer progression, and suggest that it may be a new biomarker for early diagnosis of prostate cancer.…”

“…Moreover, LINC00261 could recruit GATA6 and suppress DKK3 expression. And DKK3 can interact with miRNA and regulate Wnt/β-catenin signaling pathway [ 88 ]. Shi et al [ 34 ] also revealed that LINC00261 bound to miR-522‐3p and inhibited Wnt signaling pathway, alleviating progression of NSCLC cells.…”

“…P38 MAPK signaling pathway plays a critical role in the regulation of many cellular functions, such as cell growth, differentiation, and respond to stress and inflammatory reaction. For prostate cancer, Li et al [ 88 ] indicated that LINC00261 promoted DKK3 transcription expression by recruiting GATA6, and DKK3 could induce cellular quiescence and inhibit tumor progression through activating the p38 MAPK signaling pathway. DKK3 promoted p-p38 nuclear translocation [ 107 ] and mediated the activation of Wnt/β-catenin signaling pathway, which is closely interacted with many other signaling pathways, causing cell proliferation, migration and invasion of PCa [ 108 ].…”