NONHSAT076153

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PCGEM1 (Prostate cancer gene expression marker 1) is a long non-coding RNA (lncRNA) overexpressed in prostate cancer (PCa) cells that promotes PCa initiation and progression and protects against chemotherapy-induced apoptosis [1]. PCGEM1 has been characterized as a high-risk PCa marker and a potential biomarker for neoplasms responsive to chemoprevention by phytosterols [2].

Annotated Information

Name

PCGEM1: Prostate-specific transcript, LINC00071 (HGNC)

Characteristics

PCGEM1 is located at human chromosome 2q32.3 and spannining the genomic region of spanning the 27054 bp, consists of three exons that comprehends 1603 bp (GenBank) [3].

Function

PCGEM1 regulates expression of metabolic enzymes in multiple pathways.Expression of the metabolic genes in PCGEM1 knockdown LNCaP cell was examined by qRT-PCR. Positive and negative values indicate up and down-regulation compared with control cell, respectively.[4]

PCGEM1 regulates prostate cancer cell growth and tumor metabolism [4][1][2]. PCGEM1 regulates metabolism at a transcriptional level that affects multiple metabolic pathways, including glucose and glutamine metabolism, the pentose phosphate pathway, nucleotide and fatty acid biosynthesis, and the tricarboxylic acid cycle. The PCGEM1-mediated gene regulation takes place in part through AR activation, but predominantly through c-Myc activation, regardless of hormone or AR status. PCGEM1 binds directly to target promoters, physically interacts with c-Myc, promotes chromatin recruitment of c-Myc, and enhances its transactivation activity [4].

Over-expression of PCGEM1 leads to inhibition of apoptosis induced by doxorubicin [5]. PCGEM1 and PRNCR1 interact with the androgen receptor (AR) bound at DNA-enhancer regions in a ligand-dependent fashion and facilitate the chromosomal looping between AR-bound enhancers and the promoter sequences of androgen-responsive genes [2].

Reciprocal regulation of PCGEM1 and miR-145 promote proliferation of LNCaP prostate cancer cells and nu/nu PCa tumor growth. Both downregulation of a tumor-promoting long noncoding RNA PCGEM1 or overexpression of the tumor suppressor miR-145 reduced the proliferation and invasive capacity of prostate cancer cells in vitro and in vivo [1].

PCGEM1 is involved in the hyperplasia of the synovial lining, a common characteristic of Osteoarthritic (OA). Exogenous overexpression of PCGEM1 inhibited apoptosis, induced autophagy, and stimulated the proliferation of human synoviocytes. The increased expression of PCGEM1 in human synoviocytes also suppressed the expression of miR-770. Transfection of the miR-770 precursor resulted in reduced proliferation, and induced apoptosis of human synoviocytes [6].

Disease

  • Osteoarthritic
  • Prostate cancer

Expression

PCGEM1, was expressed exclusively in human prostate tissue, was dramatically upregulated in PCa tissues compared with normal prostate tissues. Prostate tissue-specific and prostate cancer-associated [3]. Cholesterols upregulate the expression of PCGEM1 even in androgen-insensitive prostate cancer cell lines while phytosterols reverse this effect (Ifere 2009). PCGEM1 overexpression in LNCaP and in NIH3T3 cells promotes cell proliferation and a dramatic increase in colony formation, suggesting a biological role of PCGEM1 in cell growth regulation (Petrovics 2004). Low specificity as a biomarker for prostate cancer (14%) (Bialkowska-Hobrzanska 2006). Overexpression of PCGEM1 stimulates proliferation andInhibits apoptosis of synoviocytes [6].

Experiment Forward primer Reverse primer
Quantitative PCR 5′-TGCCTCAGCCTCCCAAGTAAC-3′ 5′-GGCCAAAATAAAACCAAACAT-3′[7]
siRNA 5′-GCCCUACCUAUGAUUUCAUAU-3′ 5′-AUAUGAAAUCAUAGGUAGGGC-3′[1]
qRT-PCR 5′-CACGTGGAGGACTAAGGGTA-3′ 5′-TTGCAACAAGGGCATTTCAG-3′[1]

Regulation

p54/nrb-mediated regulation of PCGEM1[8]

p54/nrb interact with the PCGEM1 promoter and regulate PCGEM1 [8].

Allelic Information and Variation

PCGEM1 polymorphisms may contribute to PCa risk in Chinese men. Men carrying single nucleotide polymorphisms (SNPs) of PCGEM1, i.e. rs6434568 AC and rs16834898 AC, had a lower PCa risk in comparison to the ones harboring CC and AA genotypes, respectively [9].

Labs working on this lncRNA

  • State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, China.[9]
  • Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China.[9]
  • Department of Genetic Toxicology, Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.[9]
  • Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.[9]
  • Department of Environmental Genomics, School of Public Health, Nanjing Medical University, 818 East Tianyuan Road, Nanjing, Jiangsu 211166, China. [9]
  • Department of Laboratory, Central Hospital of Panyu District, 8 Fuyu Dong Road, shiqiao, Guangzhou, Guangdong 511400, P R China.[1]
  • The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510620, China.[1]
  • Department of Pharmacology and Toxicology, Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA.[8]
  • Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS, USA.[8]
  • Department of Biochemistry, Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA.[8]
  • Department of Radiation Oncology, Duke University Medical Center, Durham, NC, USA.[8]
  • System Biosciences, Mountain View, CA, USA.[8]
  • Department of Pulmonary Medicine, Tongji Hospital, Tongji University, Shanghai, China.[8]
  • Department of Pathology, University of Mississippi Medical Center, Jackson, MS, USA.[8]
  • College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, China.[8]
  • Department of Biochemistry and Molecular Medicine, Comprehensive Cancer Center, University of California at Davis, Sacramento, CA 95817.[4]
  • Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan Town, Miaoli County 350, Taiwan.[4]
  • Department of Surgery, Center for Prostate Disease Research, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799.[4]
  • Department of Biological Sciences, College of Natural Sciences, Wonkwang University, Iksan, Chunbuk 570-749, Korea.[6]
  • Department of Orthopedic Surgery, Wonkwang University School of Medicine, Iksan, Chunbuk 570-749, Korea.[6]

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 He J H, Zhang J, Han Z P, et al. Reciprocal regulation of PCGEM1 and miR-145 promote proliferation of LNCaP prostate cancer cells[J]. Journal of Experimental & Clinical Cancer Research. 2014, 33(1):72.
  2. ↑ 2.0 2.1 2.2 Martens-Uzunova ES, Böttcher R, Croce CM, Jenster G, Visakorpi T & Calin GA. Long Noncoding RNA in Prostate, Bladder, and Kidney Cancer[J]. European Urology. 2014, 65(6):1140-1151.
  3. ↑ 3.0 3.1 Srikantan V, Zou Z, Petrovics G, et al. PCGEM1, a prostate-specific gene, is overexpressed in prostate cancer[J]. Proceedings of the National Academy of Sciences. 2000, 97(22): 12216-12221.
  4. ↑ 4.0 4.1 4.2 4.3 4.4 4.5 Hung C L, Wang L Y, Yu Y L, et al. A long noncoding RNA connects c-Myc to tumor metabolism[J]. Proceedings of the National Academy of Sciences. 2014, 111(52):18697-18702.
  5. ↑ Fu X, Ravindranath L, Tran N, Petrovics G & Srivastava S. Regulation of apoptosis by a prostate-specific and prostate cancer-associated noncoding gene, PCGEM1[J]. DNA and cell biology. 2006, 25(3):135-141.
  6. ↑ 6.0 6.1 6.2 6.3 Kang Y, Song J, Kim D, et al. PCGEM1 stimulates proliferation of osteoarthritic synoviocytes by acting as a sponge for miR‐770[J]. Journal of Orthopaedic Research. 2016, 34(3):412-418.
  7. ↑ Srikantan V, Zou Z, Petrovics G, et al. PCGEM1, a prostate-specific gene, is overexpressed in prostate cancer[J]. Proceedings of the National Academy of Sciences. 2000, 97(22):12216-12221.
  8. ↑ 8.0 8.1 8.2 8.3 8.4 8.5 8.6 8.7 8.8 8.9 Ho T T, Huang J, Zhou N, et al. Regulation of PCGEM1 by p54/nrb in prostate cancer[J]. Scientific reports, 2016, 6: 34529.
  9. ↑ 9.0 9.1 9.2 9.3 9.4 9.5 Xue Y, Wang M, Kang M, et al. Association between lncrna PCGEM1 polymorphisms and prostate cancer risk[J]. Prostate cancer and prostatic diseases. 2013, 16(2):139.

Basic Information

Transcript ID

NONHSAT076153

Source

NONCODE4.0

Same with

,

Classification

intergenic

Length

1603 nt

Genomic location

chr2+:193614571..193641625

Exon number

3

Exons

193614571..193614754,193615515..193615598,193640304..193641625

Genome context

Sequence

>gi

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