Overexpression of H19 in malignant tissues compared to adjacent non-malignant tissues marks H19 as an independent prognostic marker in CRC. Besides its prognostic value, H19 serves as a promising target for therapy in CRC treatment.
Spatial transcriptomics and single-nucleus RNAseq analyses identify a 60-gene signature in 11p15.5 altered hepatocytes. These data provide insights for 11p15.5 mosaicism detection and its functional consequences during the early steps of carcinogenesis.
Consistently, blockage of miR-107 activity alleviated the growth suppression phenotypes induced by H19 downregulation, suggesting that H19 serves as a molecular sponge for miR-107 to promote CDK6 expression and cell cycle progression. Together, this study demonstrates a mechanistic function of H19 in driving the proliferation of HCC cells and suggests H19 suppression as a novel approach for HCC treatment.
HIF-1α induced overexpression of H19 via binding with the promoter of H19, and H19 promoted GC cells proliferation, migration and angiogenesis through YTHDF1/SCARB1, which might be a beneficial target for antiangiogenic therapy for GC.
The high level of H19 enhanced the cytotoxicity of erlotinib by inducing ferroptosis. In conclusion, our data showed that β-elemene combined with erlotinib could enhance sensitivity to EGFR-TKIs through induction of ferroptosis via H19 in primary EGFR-TKI-resistant lung cancer, providing a promising strategy to overcome EGFR-TKI resistance in NSCLC patients.
H19 over-expression may induce the elevated expression of mtp53 and interact with mtp53, leading to LAC progression. In addition, the high expression of mtp53 R175H is associated with poor overall survival inpatients. The simultaneous inhibition of H19 and mtp53 may provide a novel strategy for the effective control of LAC clinically.
These results suggest that HHLA2 overexpression can promote GBC progression. Conversely, ablation of HHLA2 expression inhibited both TGF‑β1‑ and lncRNA H19‑induced GBC progression, suggesting that HHLA2 is a potential therapeutic target for this disease.
At last, we found that overexpression of exosomal H19 from TAMs suppressed the interaction between ULK1 and its specific E3 ligase NEDD4L in BC cells. We revealed the effect of TAMs-exo-contained lncRNA H19 on regulating autophagy of bladder cancer cells, which indicated that targeting TAMs-H19 is a promising therapeutic strategy for the treatment of BC.
LncRNA-H19 expression was increased in CSCs, in liver tissue and plasma of patients with HCC and decreased after partial/complete therapeutic response. Those patients who developed HCC during the follow-up showed higher levels of lncRNA-H19. LncRNA-H19 could constitute a new biomarker of HCC.
In conclusion, our data show that the natural product curcumenol exerted its antitumor effects on lung cancer by triggering ferroptosis, and the lncRNA H19/miR-19b-3p/FTH1 axis plays an essential role in curcumenol-induced ferroptotic cell death. Therefore, our findings will hopefully provide a valuable drug for treating lung cancer patients.
The key finding of the present study suggests that overexpression of H19 may be associated with an unfavorable prognosis for OC and is likely to be a possible contributory force involved in OC cell migration and invasion. H19 may provide a new and attractive target for future prognostic and therapeutic intervention of OC patients.
Our clinical data identify H19 as a candidate diagnostic marker and predictive marker of NEPC with elevated H19 levels associated with an increased probability of biochemical recurrence and metastatic disease in patients receiving ADT. Here we report H19 as an early upstream regulator of cell fate, plasticity, and treatment resistance in NEPC that can reverse/transform cells to a treatable form of PCa once therapeutically deactivated.
The administration of the deacetylase inhibitors (DACi) panobinostat, trichostatin A and SAHA affected the cell viability of H295R monolayer and spheroids and induced the over-expression of H19 and autophagy transcripts...Neither the active protein level nor the activity of caspases 8 and 3 was prompted by the DACi, thus excluding the involvement of the executioners of apoptosis in H295R decay.The deacetylase inhibitors restore H19, the autophagy markers and trigger cell death in adrenocortical carcinoma cells. The re-activation of autophagy would represent a novel strategy for the treatment of patients affected by this severe malignancy.
It could be concluded that H19 competitively bound to miR-149-5p to upregulate LIF expression and activate the PI3K/Akt pathway, thus reducing cardiomyocyte apoptosis in neonatal rats with HIBD. This study may offer new insights for HIBD treatment.
Moreover, overexpression promoted tumor growth in nude mice and was suppressed by PI3K inhibitor. LncRNA H19 downregulation of miR-140-5p to activate the PI3K/AKT signaling pathway and promote the proliferation, invasion, migration and EMT of OC.
Colon cancer H19 expression is associated with advanced stage of tumor disease and is a significant risk factor for reduced recurrence-free survival. Tumor expression of H19 may have potential for both prognostic and therapeutic uses in the future.
Median progression-free survival was 35 months (for 11 patients with data available). In summary, our findings suggest the existence of a novel group of supratentorial neuroepithelial tumors that are characterized by recurrent PLAGL1 fusions and enriched for pediatric patients.
Moreover, conditioned medium (CM) from stable knockdown H19 GC cells modulated the activity of immune cells including γδT cells, Jurkat cells, and tumor-associated macrophages (TAMs) in a miR-519d-3p/LDHA/lactate axis dependent manner. The H19/miR-519d-3p/LDHA axis mainly contributed to aerobic glycolysis, proliferation, and immune escape of GC cells.
Lastly, we demonstrate that arecoline stimulated the upregulation of H19 through the transforming growth factor (TGF)-β pathway. Altogether, this study suggests that increased TGF-β secretion following areca nut chewing may induce the upregulation of H19, which serves as a natural sponge for miR-29b and impedes its antifibrotic effects.
In terms of the mechanism, knockdown of H19 inhibited cell proliferation, migration and invasion, while overexpression of H19 reversed the inhibitory effect of Rg3 on the OC cells. In conclusion, ginsenoside Rg3 suppresses the proliferation, migration and invasion of OC cells by partially inhibiting the expression of lncRNA H19.
H19 overexpression decreased miR-107 and increased VEGF expression, which resulted in repressed neuronal apoptosis and alleviated cognitive dysfunction. Thus, H19 may serve as a molecular target for translational research for HIBD therapy.
H19 promoted proliferation, migration, and autophagy by regulating mTOR signaling. In conclusion, we validate that H19 contributes to the proliferation and autophagy of glioma cells through the mTOR/ULK1 pathway.
Conversely, the genetic silencing of H19 or miR‑675 inhibited proliferation and invasion in SCL1 and A431 cSCC cell lines. In conclusion, the findings of the present study provided novel insight into the potential role of H19 and miR‑675 in the development, metastasis and progression of cSCC, which may help the development of treatments for cSCC.
Additionally, H19 enhanced cell migration and invasion by upregulating zinc finger E-box binding homeobox 1 (ZEB1) via the sequestration of miR-200b-3p. H19 plays a critical role in HCC bone metastasis by reducing OPG expression, which is mediated by the PPP1CA-induced inactivation of the p38MAPK pathway, and H19 also functions as a sponge for miR-200b-3p.
H19 can be used as a biological indicator for diagnosing GC and predicting patients' poor prognosis. Additionally, it promotes GCCs to proliferate and invade through miR-138/E2F2 axis.
FOXF2 was upregulated in NSCLC. It accelerated the proliferative and migratory abilities of the NSCLC cells by targeting H19 to downregulate PTEN, thus aggravating the progression of NSCLC.
The present study indicated that H19 may serve as a promoting factor of EMT, invasion and migration in MCF‑7/TAMR cells, suggesting that curcumin may prevent H19‑associated metastasis. Therefore, curcumin may serve as a promising therapeutic drug for patients with TAMR breast cancer.
Lnc-RNA H19 overexpression plasmid pcdna3.1-h19 and Akt overexpression plasmid pcdna3.1-akt decreased apoptosis in RPMI 8226 cell lines without VCR resistance (***p<0.001), while the recombination of siRNA-h19 and siRNA-akt plasmid increased apoptosis in RPMI 8226-VCR (***p<0.001). The lnc-RNA H19/Akt pathway is closely related to the occurrence of VCR resistance in MM cells, and the down-regulation of H19 can significantly improve the sensitivity of VCR in MM.
Overexpression of miR-612 could rescue the proliferation, migration and invasion of cholangiocarcinoma cells caused by lncRNA H19 overexpression. Taken together, HIF1α activated lncRNA H19-mediated miR-612/Bcl-2 pathway to promote cholangiocarcinoma, suggesting a promising therapeutic target for cholangiocarcinoma.
Cancer cell migration and invasion were not significantly affected by PTCSC3 overexpression. Therefore, lncRNA PTCSC3 inhibits TNBC cell proliferation by downregulating lncRNA H19.
Besides, bioinformatics tools and dual-luciferase reporters assays indicated that miR-340-3p could act as a potential target gene of H19, the underlying mechanism studies proved that H19 could act as a competing endogenous RNA (ceRNA) via competitively binding miR-340-3p to promote BC cell proliferation, metastasis and EMT by regulating tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) and potentiate the Wnt/β-catenin signaling in BC cells. In summary, our findings demonstrated that H19 could act as a ceRNA in BC progression, metastasis and EMT through modulating miR-340-3p/YWHAZ axis and activating the canonical Wnt/β-catenin signaling pathway, indicating that H19 might act as an underlying therapeutic target and prognostic biomarker for BC therapy.