Abstract
Long noncoding RNA H19 (H19) is an imprinting gene with only maternal expression that is involved in regulating different processes in various types of cells. Previous studies have shown that abnormal H19 expression is involved in many pathological processes, such as cancer, mainly through sponging miRNAs, interacting with proteins, or regulating epigenetic modifications. Accumulating evidence has shown that several oncogenic signaling pathways lead to carcinogenesis. Recently, the regulatory relationship between H19 and oncogenic signaling pathways in various types of cancer has been of great interest to many researchers. In this review, we discussed the key roles of H19 in cancer development and progression via its regulatory function in several oncogenic signaling pathways, such as PI3K/Akt, canonical Wnt/β-catenin, canonical NF-κB, MAPK, JAK/STAT and apoptosis. These oncogenic signaling pathways regulated by H19 are involved in cell proliferation, proliferation, migration and invasion, angiogenesis, and apoptosis of various cancer cells. This review suggests that H19 may be a novel therapeutic target for cancers treatment by regulating oncogenic signaling pathways.
Highlights
In human genomic, only 2% of all human genes are protein coding genes, while the 98% genes are transcribed into non-coding RNA
This review suggests that H19 may be a novel therapeutic target for cancers treatment by regulating oncogenic signaling pathways
We provide important clues for understanding the key roles of the H19 functional network in signaling pathways and identifying new therapeutic targets for several cancers (Figure 1), such as gastric cancer, hepatocellular carcinoma (HCC), pancreatic cancer, colorectal cancer (CRC), breast cancer, thyroid cancer, non-small cell lung cancer (NSCLC), melanoma, Hodgkin’s lymphoma, choriocarcinoma, glioma, bladder cancer, osteosarcoma, multiple myeloma (MM), and oral and cholangiocarcinoma
Summary
Only 2% of all human genes are protein coding genes, while the 98% genes are transcribed into non-coding RNA (ncRNA). H19 can interact with other miRNAs, such as miR-326 (Wei et al, 2019), miR-29a (Cheng et al, 2019), miR-124-3p (Liu et al, 2019), miR-152-3p (Zheng et al, 2020), miR-22-3p (Gan et al, 2019), miR-29b-3p (Zhong et al, 2021), miR-193a-3p (Ma et al, 2018), miR-612 (Yu et al, 2020), to regulate biological processes in various types of cells by modulating the expression of downstream target factors, including twist family bHLH transcription factor 1 (TWIST1), thymine DNA glycosylase, integrin β3 (ITGB3), bromodomain containing protein 4 (BRD4), Snail, high mobility group box 1 (HMGB1), presenilin-1 (PSEN1), and Bcl-2. H19 can participate in epigenetic regulation to regulate gene expression by recruiting epigenetic regulatory factors involved in histone methylation (Alipoor et al, 2020) Under pathological processes, such as cancer, H19 can be reexpressed. We provide important clues for understanding the key roles of the H19 functional network in signaling pathways and identifying new therapeutic targets for several cancers (Figure 1), such as gastric cancer, hepatocellular carcinoma (HCC), pancreatic cancer, colorectal cancer (CRC), breast cancer, thyroid cancer, non-small cell lung cancer (NSCLC), melanoma, Hodgkin’s lymphoma, choriocarcinoma, glioma, bladder cancer, osteosarcoma, multiple myeloma (MM), and oral and cholangiocarcinoma
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