The long noncoding RNA H19 promotes cell proliferation via E2F-1 in pancreatic ductal adenocarcinoma

Ma, Ling; Tian, Xiaodong; Wang, Feng; Zhang, Zhengkui; Du, Chong; Xie, Xing; Kornmann, Marko; Yang, Yue

doi:10.1080/15384047.2016.1219814

Cited by 70 publications

(60 citation statements)

References 29 publications

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“…For example, Ma et al reported that H19 promotes proliferation of pancreatic ductal adenocarcinoma cells [24]. Yang et al showed that overexpression of H19 increases cell proliferation and decreases apoptosis of gastric cancer cells [25].…”

Section: Discussionmentioning

confidence: 99%

Long Non-Coding RNA H19 Protects H9c2 Cells against Hypoxia-Induced Injury by Targeting MicroRNA-139

Gong¹,

Xu²,

Guo³

et al. 2017

Cell Physiol Biochem

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Background/Aims: Acute myocardial infarction (AMI) occurs when blood supply to the heart is diminished (ischemia) for long time; ischemia is primarily caused due to hypoxia. The present study evaluated the effects of long non-coding RNA H19 on hypoxic rat H9c2 cells and mouse HL-1 cells. Methods: Hypoxic injury was confirmed by measuring cell viability, migration and invasion, and apoptosis using MTT, Transwell and flow cytometry assays, respectively. H19 expression after hypoxia was estimated by qRT-PCR. We then measured the effects of non-physiologically expressed H19, knockdown of miR-139 with or without H19 silence, and abnormally expressed Sox8 on hypoxia-induced H9c2 cells. Moreover, the interacted miRNA for H19 and downstream target gene were virtually screened and verified. The involved signaling pathways and the effects of abnormally expressed H19 on contractility of HL-1 cells were explored via Western blot analysis. Results: Hypoxia induced decreases of cell viability, migration and invasion, increase of cell apoptosis and up-regulation of H19. Knockdown of H19 increased hypoxia-induced injury in H9c2 cells. H19 acted as a sponge for miR-139 and H19 knockdown aggravated hypoxia-induced injury by up-regulating miR-139. Sox8 was identified as a target of miR-139, and its expression was negatively regulated by miR-139. The mechanistic studies revealed that overexpression of Sox8 might decrease hypoxia-induced cell injury by activating the PI3K/AKT/mTOR pathway and MAPK. Besides, H19 promoted contractility of HL-1 cells. Conclusion: These findings suggest that H19 alleviates hypoxia-induced myocardial cell injury by miR-139-mediated up-regulation of Sox8, along with activation of the PI3K/AKT/mTOR pathway and MAPK.

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Section: Discussionmentioning

confidence: 99%

Long Non-Coding RNA H19 Protects H9c2 Cells against Hypoxia-Induced Injury by Targeting MicroRNA-139

Gong¹,

Xu²,

Guo³

et al. 2017

Cell Physiol Biochem

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“…The lncRNA H19 is an estrogen‐regulated gene whose expression is suppressed in adult liver . Aberrant expression of H19 has been associated with various cancers . H19 is also up‐regulated in BDL mice .…”

Section: Resultsmentioning

confidence: 99%

The role of long noncoding RNA H19 in gender disparity of cholestatic liver injury in multidrug resistance 2 gene knockout mice

Liu

Yang

et al. 2017

Hepatology

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The multi-drug resistance 2 knockout (Mdr2−/−) mouse is a well-established model of cholestatic cholangiopathies. Female Mdr2−/− mice develop more severe hepatobiliary damage than male Mdr2−/− mice, which is correlated with a higher proportion of taurocholate (TCA) in bile. Although estrogen has been identified as an important player in intrahepatic cholestasis, the underlying molecular mechanisms of gender-based disparity of cholestatic injury remain unclear. The long non-coding RNA H19 is an imprinted, maternally expressed and estrogen-targeted gene, which is significantly induced in human fibrotic/cirrhotic liver and bile duct ligated mouse liver. However, whether aberrant expression of H19 accounts for gender-based disparity of cholestatic injury in Mdr2−/− mice remains unknown. The current study demonstrated that H19 was markedly induced (~200-fold) in the livers of female Mdr2−/− mice at advanced stages of cholestasis (100-day-old), but not in aged-matched male Mdr2−/− mice. During the early stages of cholestasis, H19 expression was minimal. We further determined that the hepatic H19 was mainly expressed in cholangiocytes, not hepatocytes. Both TCA and estrogen significantly activated the ERK1/2 signaling pathway and induced H19 expression in cholangiocytes. Knocking down H19 not only significantly reduced TCA/estrogen-induced expression of fibrotic genes and sphingosine 1-phosphate receptor 2 (S1PR2) in cholangiocytes, but also markedly reduced cholestatic injury in female Mdr2−/− mice. Furthermore, the expression of small heterodimer partner was substantially inhibited at advanced stages of liver fibrosis, which was reversed by H19 shRNA in female Mdr2−/− mice. Similar findings were obtained in human PSC liver samples. Conclusion H19 plays a critical role in the disease progression of cholestasis and represents a key factor that causes the gender disparity of cholestatic liver injury in Mdr2−/− mice.

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“…In accordance with the previous studies, H19 downregulation was found to inhibit cell proliferation and invasion of breast cancer cells, indicating that H19 acted as an oncogene and upregulation of H19 played a crucial role in breast cancer. Consistently, H19 was highly expressed and played oncogenic role by promoting cell proliferation in cervical cancer and pancreatic ductal adenocarcinoma . Thus, H19 may act as a potential biomarker and therapeutic target for breast cancer progression and diagnosis.…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA H19 promotes the proliferation and invasion of breast cancer through upregulating DNMT1 expression by sponging miR-152

et al. 2017

J Biochem Mol Toxicol

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Long non-coding RNA (lncRNA) H19 in tumors played important roles in various biological processes. However, the biological role and molecular mechanism of H19 in breast cancer are unclear. Here, we found that H19 was aberrantly upregulated in human breast tumor tissues and cells. A negative correlation between H19 and miR-152 and positive correlation between H19 and DNMT1 mRNA were observed. Downregulation of H19 and DNMT1 significantly retarded breast cancer cell proliferation and invasion. H19 act as an endogenous sponge by directly binding to miR-152. miR-152 directly targeted DNMT1 and was regulated by H19. Besides, H19 overexpression dramatically relieved the inhibition of miR-152 on DNMT1 expression. miR-152 inhibition and DNMT1 overexpression obviously reversed the inhibitory effects of H19 downregulation on cell proliferation and invasion. In conclusion, H19 promoted proliferation and invasion of breast cancer through the miR-152/DNMT1 axis, providing a novel mechanism about the occurrence and development of breast cancer.

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The long noncoding RNA H19 promotes cell proliferation via E2F-1 in pancreatic ductal adenocarcinoma

Cited by 70 publications

References 29 publications

Long Non-Coding RNA H19 Protects H9c2 Cells against Hypoxia-Induced Injury by Targeting MicroRNA-139

Long Non-Coding RNA H19 Protects H9c2 Cells against Hypoxia-Induced Injury by Targeting MicroRNA-139

The role of long noncoding RNA H19 in gender disparity of cholestatic liver injury in multidrug resistance 2 gene knockout mice

Long non-coding RNA H19 promotes the proliferation and invasion of breast cancer through upregulating DNMT1 expression by sponging miR-152

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