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Tumor Biology

, Volume 37, Issue 12, pp 16163–16176 | Cite as

Snail-activated long non-coding RNA PCA3 up-regulates PRKD3 expression by miR-1261 sponging, thereby promotes invasion and migration of prostate cancer cells

  • Jin-Hua He
  • Bao-Xia Li
  • Ze-Ping Han
  • Mao-Xian Zou
  • Li Wang
  • Yu-Bing Lv
  • Jia-Bin Zhou
  • Ming-Rong Cao
  • Yu-Guang Li
  • Jing-zhi Zhang
Original Article

Abstract

Rapidly accumulated evidence has shown that long non-coding RNA (lncRNAs) disregulation is involved in human tumorigenesis in many cancers, including prostate cancer (PCa). LncRNAs can regulate essential pathways that contribute to tumor initiation and progression with tissue specificity, which suggests that lncRNAs could be valuable biomarkers and therapeutic targets. Prostate cancer antigen 3 (PCA3), also known as differential display code 3 (DD3), is one such lncRNA that maps to chromosome 9q21–22. PCA3 expression is highly specific to PCa. In the present study, the level of PCA3 expression in prostate cancer cells was reduced by small interfering RNA (siRNA). Subsequently, the ability of LNCaP cell proliferation, invasion, and migration of PCa was compromised both in vivo and in vitro with the occurrence of cell autophagy. Recently, a novel regulatory mechanism has been proposed in which RNAs cross talk via competing with the shared microRNAs (miRNAs). In addition, lncRNAs can directly interact with RNA-binding proteins and then bind to the gene promoter region to further regulate gene expression. The proposed competitive endogenous RNAs mediate the bioavailability of miRNAs on their targets, thus imposing another level of post-transcriptional regulation. Here, we demonstrated that binding of Snail to the promoter region of PCA3 could activate the expression of PCA3. Down-regulation of PCA3 by silencing could increase the expression of the miRNA-1261, which then targeted at the PRKD3 gene (protein kinase D3) through competitive sponging. In summary, these results suggest that the transcription factor, Snail, activated the expression of lncRNA PCA3, which could inhibit the translation of PRKD3 protein via competitive miR-1261 sponging, and thus high expression of PRKD3 further promoted invasion and migration of prostate cancer.

Keywords

Long non-coding RNA microRNA-1261 Differential display code 3 Protein kinase D3 Prostate cancer cells Small interfering RNA sequences 

Abbreviations

lncRNA

Long non-coding RNA

miRNA

microRNA

siRNA

Small interfering RNA

WST-8

Cell counting kit-8

PCGEM1

Prostate cancer gene expression marker 1

FBS

Fetal bovine serum

MALAT-1

Metastasis-associated lung adenocarcinoma transcript

PCA3

Prostate cancer antigen 3

CRPC

Castration-refractory prostate cancer

TF

Transcription factor

LC3

Microtubule-associated protein 1 light chain 3

PRKD3

Protein kinase D3

MEG3

Maternally-expressed gene 3

PRC2

Polycomb repressive complex 2

RT-PCR

Reverse transcription polymerase chain reaction

HRP

Horseradish peroxidase

TFs

Transcription factors

Pca

Prostate cancer

3′ UTR

3 terminal untranslated region

shRNA

Small hair RNA

ceRNA

Competing endogenous RNA

Notes

Acknowledgments

This work was supported by grants from the Technical New Star of Zhujiang, Pan Yu districts, Guangzhou (No. 2014-special-15-3.09 and No:2013-special-15-6.09) and the Natural Science Foundation of China (No.81373520; No.81502557); the Administration of Traditional Chinese Medicine of Guangdong Province (20151057) and the Science and Technology Planning Project of Guangdong Province (No. 2015110); and the technology projects of Guangzhou medicine and health care (No.2016A011112).

Compliance with ethical standards

Conflicts of interest

None.

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Jin-Hua He
    • 1
  • Bao-Xia Li
    • 2
  • Ze-Ping Han
    • 1
  • Mao-Xian Zou
    • 1
  • Li Wang
    • 1
  • Yu-Bing Lv
    • 1
  • Jia-Bin Zhou
    • 1
  • Ming-Rong Cao
    • 3
  • Yu-Guang Li
    • 1
  • Jing-zhi Zhang
    • 4
  1. 1.Department of LaboratoryCentral Hospital of Panyu DistrictGuangzhouChina
  2. 2.State Key Laboratory of Oncology in South ChinaSun Yat-sen University Cancer CenterGuangzhouChina
  3. 3.Department of General Surgery, First Affiliated HospitalJinan UniversityGuangzhouChina
  4. 4.The Second Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina

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