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Review
. 2017 Feb 20;18(2):450.
doi: 10.3390/ijms18020450.

The Interplay of LncRNA-H19 and Its Binding Partners in Physiological Process and Gastric Carcinogenesis

Li Zhang  1 , Yuhang Zhou  2   3   4   5 , Tingting Huang  6   7   8   9 , Alfred S L Cheng  10   11   12 , Jun Yu  13   14   15 , Wei Kang  16   17   18   19 , Ka Fai To  20   21   22   23
Affiliations
Review

The Interplay of LncRNA-H19 and Its Binding Partners in Physiological Process and Gastric Carcinogenesis

Li Zhang et al. Int J Mol Sci. .

Abstract

Long non-coding RNA (lncRNA), a novel and effective modulator in carcinogenesis, has become a study hotspot in recent years. The imprinted oncofetal lncRNA H19 is one of the first identified imprinted lncRNAs with a high expression level in embryogenesis but is barely detectable in most tissues after birth. Aberrant alterations of H19 expression have been demonstrated in various tumors, including gastric cancer (GC), implicating a crucial role of H19 in cancer progression. As one of the top malignancies in the world, GC has already become a serious concern to public health with poor prognosis. The regulatory roles of H19 in gastric carcinogenesis have been explored by various research groups, which leads to the development of GC therapy. This review comprehensively summarizes the current knowledge of H19 in tumorigenesis, especially in GC pathogenesis, with emphasis on the underneath molecular mechanisms depicted from its functional partners. Furthermore, the accumulated knowledge of H19 will provide better understanding on targeted therapy of GC.

Keywords: H19; gastric cancer; lncRNA.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
H19 associated proteins. Different associated proteins of H19 reported up to date are shown. These proteins are involved in various biological processes as indicated in the outward cycle. Most of them are RNA binding proteins (KSRP, IMP-1, HuR and HnRNP U) and DNA/chromatin modification factors (SAHH, PRC2 and MBD1), suggesting of a crucial role of H19 on gene expression. P53 and ISM1 have been identified as associated proteins of H19 in GC. PTBP1, another RNA binding protein, has also identified as one of H19 interaction proteins with unclear function. GC, gastric cancer.
Figure 2
Figure 2
H19 interactive miRNAs. Different associated miRNAs of H19 are demonstrated. These four miRNAs are involved in several kinds of cancers and development via targeting functional factors as indicated in tables. In GC, H19 associates with miR-141 and further affects downstream targets: miR-675, IGF1R, IGF2, Drosha, Dicer and ZEB1. EMT, epithelial–mesenchymal transition; CRC, colorectal cancer; GC, gastric cancer.
Figure 3
Figure 3
Summary of direct targets of H19/miR-675 axis in different cancer types. H19/miR-675 suppresses prostate cancer metastasis via decreasing TGFB1; enhances tumorigenesis and metastasis of breast cancer by downregulating c-Cbl and Cbl-b; promotes colorectal cancer via decreasing tumor suppressor, RB; mediates AFP-secreting HCC as oncogene via decreasing RB and Twist 1; increases tumorigenesis potential of glioma via targeting Cadherin 13 and CDK6; modulates NSCLC development as a tumor suppressor via targeting GPR55; promotes gastric tumorigenesis through targeting RUNX1 and CALN1. RB, retinoblastoma protein; HCC, hepatocellular carcinoma; NSCLC, non-small cell lung carcinoma.
Figure 4
Figure 4
Summary of molecular mechanisms of H19 in GC development. On the one hand, miR-675 derived from H19 can target and degrade RUNX1 and CALN1 mRNA to enhance GC development via influencing potential signaling pathways. On the other hand, H19 binds with p53 to inhibit its activity and decrease BAX. H19 can also bind to ISM1 to induce ISM1 stabilization. The downregulation of miR-141 and c-Myc activation can up-regulate H19 expression in gastric tumorigenesis. GC, gastric cancer; up arrow, upregulation; down arrow, downregulation.
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