The role of the oncofetal H19 lncRNA in tumor metastasis: orchestrating the EMT-MET decision

Matouk, Imad; Halle, David; Raveh, Eli; Gilon, Michal; Sorin, Vera; Hochberg, Avraham

doi:10.18632/oncotarget.6387

Cited by 122 publications

(97 citation statements)

References 109 publications

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“…37,50 Here, I report that TGF-b1 treatment strongly upregulated H19 expression in HeLa cells while CoCl 2 , a hypoxia-mimetic agent, increased H19 expression in MS751 cells (Figure 6(b) and (c)). Interestingly, downregulation of H19 expression upon TGF-b1 treatment was evident in both SiHa and MS751 cell lines (Figure 6(b)), suggesting that H19 might function primarily as a MET inducer in these cell lines.…”

Section: Discussionmentioning

confidence: 79%

Long non-coding RNA H19 enhances cell proliferation and anchorage-independent growth of cervical cancer cell lines

Iempridee

2016

Exp Biol Med (Maywood)

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Long non-coding RNA H19 is aberrantly expressed in multiple malignancies and its expression levels correlate with recurrence, metastasis, and patient survival. Despite numerous reports documenting the role of H19 in carcinogenesis, its contribution to cervical cancer development is still largely unknown. In this study, I observed that H19 expression was elevated in cervical cancer cell lines and could be detected in extracellular vesicles in the culture medium. In addition, I demonstrated, by overexpression and knockdown experiments, that H19 promoted cell proliferation and multicellular tumor spheroid formation without significantly affecting apoptosis and cell migration. Finally, treatment with transforming growth factor beta and hypoxia-mimetic CoCl 2 could modulate H19 levels in a cell line-specific manner. These findings indicate that H19 promotes both anchorage-specific andindependent growth of cervical cancer cell lines and may serve as a potential target for cancer diagnosis and therapy.

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Section: Discussionmentioning

confidence: 79%

Long non-coding RNA H19 enhances cell proliferation and anchorage-independent growth of cervical cancer cell lines

Iempridee

2016

Exp Biol Med (Maywood)

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“…LncRNA H19 level is up-regulated in patients with nuclear ARC in a disease developmentdependent manner H19 has been reported to play important roles in many biological processes, such as cellular differentiation, proliferation and stress tolerance [24,25].We determined the correlation between H19 expression and nuclear ARC occurrence. The demographic and clinical features of nuclear ARC patients and age-matched controls for qRT-PCR detection are shown in Table 2.…”

Section: Differential Lncrna Expression Between Transparent and Nuclementioning

confidence: 99%

“…Cellular Physiology and Biochemistry revealed that CRYAA, an important gene encoding the predominant structural proteins involved in the maintenance of lens clarity and refractive properties [24], was a binding target of miR-675 (Fig. 4C).…”

Section: Cellular Physiology and Biochemistrymentioning

confidence: 99%

Long Non-Coding RNA H19 Regulates Human Lens Epithelial Cells Function

Liu

Shan

et al. 2018

Cell Physiol Biochem

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Background/Aims: Age-related cataract (ARC) remains the leading cause of visual impairment among the elderly population. Long non-coding RNAs (lncRNAs) have emerged as potential regulators in many ocular diseases. However, the role of lncRNAs in nuclear ARC, a subtype of ARC, requires further elucidation. Methods: LncRNA sequencing was performed to identify differentially expressed lncRNAs between the capsules of transparent and nuclear ARC lenses. Expression validation was confirmed by qRT-PCR. MTT assay, Calcein-AM and propidium iodide double staining, Rhodamine 123 and Hoechst double staining, EdU and transwell assay were used to determine the role of H19 or miR-675 in the viability, apoptosis, proliferation and migration of primary cultured human lens epithelial cells (HLECs). Bioinformatics and luciferase reporter assays were used to identify the binding target of miR-675. Results: Sixty-three lncRNAs are differentially expressed between the capsules of transparent and nuclear ARC lenses. One top abundantly expressed lncRNA, H19, is significantly up-regulated in the nuclear ARC lens capsules and positively associated with nuclear ARC grade. H19 knockdown accelerates apoptosis development and reduces the proliferation and migration of HLECs upon oxidative stress. H19 is the precursor of miR-675, and a reduction of H19 inhibits miR-675 expression. miR-675 regulates CRYAA expression by targeting the binding site within the 3’UTR. Moreover, miR-675 increases the proliferation and migration while decreasing the apoptosis of HLECs upon oxidative stress. Conclusion: H19 regulates HLECs function through miR-675-mediated CRYAA expression. This finding would provide a novel insight into the pathogenesis of nuclear ARC.

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“…Thus, gastric cancer is a threat to global health. It has been documented that the invasion and metastasis of tumor cells is a major cause of mortality in patients with cancer (5). Clinical evidence has also indicated that the prognosis of gastric cancer is associated with the stage of disease at diagnosis, with early diagnosis of gastric cancer resulting in a lower incidence of metastasis and a five-year survival rate of >90% (6).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-421 promotes the proliferation and metastasis of gastric cancer cells by targeting claudin-11

Yang

Mei

Liu

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. The present study aimed to evaluate the expression of microRNA (miR)-421 in gastric cancer and to investigate its biological function and underlying mechanism of action in the development of gastric cancer. The expression of miR-421 was measured in 60 pairs of clinically removed gastric cancer tissues and matched adjacent normal gastric tissues by reverse transcription-quantitative polymerase chain reaction. In addition, following transfection with an miR-421 inhibitor to suppress the expression of miR-421, the proliferation, migration and cell cycle distribution of human gastric carcinoma MKN28/MKN74 cells were determined by cell counting, Transwell and flow cytometry assays. The target gene of miR-421 was also predicted using bioinformatic analysis and verified by dual-luciferase reporter gene assay and western blot analysis. Furthermore, overexpression of the miR-421 target protein was induced in MKN28/MKN74 cells to determine its function. It was observed that miR-421 was significantly upregulated in gastric cancer tissues and that the expression of miR-421 was associated with lymph node metastasis and the clinical stage of gastric cancer (all P<0.05). Claudin11 (CLDN11) was predicted and verified as a direct target of miR-421. In vitro experiments demonstrated that inhibition of miR-421 expression suppressed the proliferation and metastasis of MKN28/MKN74 cells and induced G1/S-phase cell cycle arrest (all P<0.05). Analagous results were observed in MKN28/MKN74 cells following overexpression of the CLDN11 protein. Collectively, these data suggest that miR-421 may promote the proliferation, invasion and metastasis of gastric cancer by inhibiting the expression of CLDN11.

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The role of the oncofetal H19 lncRNA in tumor metastasis: orchestrating the EMT-MET decision

Cited by 122 publications

References 109 publications

Long non-coding RNA H19 enhances cell proliferation and anchorage-independent growth of cervical cancer cell lines

Long non-coding RNA H19 enhances cell proliferation and anchorage-independent growth of cervical cancer cell lines

Long Non-Coding RNA H19 Regulates Human Lens Epithelial Cells Function

MicroRNA-421 promotes the proliferation and metastasis of gastric cancer cells by targeting claudin-11

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