scholarly journals LINK-A Long Non-Coding RNA (lncRNA) Participates in Metastasis of Ovarian Carcinoma and Upregulates Hypoxia-Inducible Factor 1 (HIF1α)

2019 ◽  
Vol 25 ◽  
pp. 2221-2227 ◽  
Author(s):  
Huijun Zhang ◽  
Bin Yao ◽  
Shengchun Tang ◽  
Ying Chen
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Fang Zheng ◽  
Jianing Chen ◽  
Xiaoqian Zhang ◽  
Zifeng Wang ◽  
Jiewen Chen ◽  
...  

AbstractHypoxia-inducible factor-1 (HIF-1) is a master driver of glucose metabolism in cancer cells. Here, we demonstrate that a HIF-1α anti-sense lncRNA, HIFAL, is essential for maintaining and enhancing HIF-1α-mediated transactivation and glycolysis. Mechanistically, HIFAL recruits prolyl hydroxylase 3 (PHD3) to pyruvate kinase 2 (PKM2) to induce its prolyl hydroxylation and introduces the PKM2/PHD3 complex into the nucleus via binding with heterogeneous nuclear ribonucleoprotein F (hnRNPF) to enhance HIF-1α transactivation. Reciprocally, HIF-1α induces HIFAL transcription, which forms a positive feed-forward loop to maintain the transactivation activity of HIF-1α. Clinically, high HIFAL expression is associated with aggressive breast cancer phenotype and poor patient outcome. Furthermore, HIFAL overexpression promotes tumor growth in vivo, while targeting both HIFAL and HIF-1α significantly reduces their effect on cancer growth. Overall, our results indicate a critical regulatory role of HIFAL in HIF-1α-driven transactivation and glycolysis, identifying HIFAL as a therapeutic target for cancer treatment.


2020 ◽  
Vol 21 (15) ◽  
pp. 5237 ◽  
Author(s):  
Natalie Filippov-Levy ◽  
Reuven Reich ◽  
Ben Davidson

The objective of the present study was to analyze the biological and clinical role of the long non-coding RNA LOC642852 in ovarian carcinoma (OC). LOC642852 expression was analyzed in seven OC cell lines (OVCAR-3, OVCAR-8, OVCA 433, OVCA 429, OC 238, DOV13, ES-2) and 139 high-grade serous carcinoma (HGSC) specimens (85 effusions, 54 surgical specimens). Following LOC642852 knockout (KO) using the CRISPR/Cas9 system, OVCAR-8 HGSC cells were analyzed for spheroid formation, migration, invasion, proliferation, matrix metalloproteinase (MMP) activity, and expression of cell signaling proteins. OVCAR-8 cells with LOC642852 KO were significantly less motile and less invasive compared to controls, with no differences in spheroid formation, proliferation, or matrix metalloproteinase (MMP) activity. Total Akt and Erk levels were comparable in controls and KO cells, but their phosphorylation was significantly increased in the latter. In clinical specimens, LOC642852 was overexpressed in ovarian tumors and omental/peritoneal metastases compared to effusion specimens (p = 0.013). A non-significant trend for shorter overall (p = 0.109) and progression-free (p = 0.056) survival was observed in patients with HGSC effusions with high LOC642852 levels. Bioinformatics analysis showed potential roles for LOC642852 as part of the TLE3/miR-221-3p ceRNA network and in relation to the FGFR3 protein. In conclusion, LOC642852 inactivation via CRISPR/Cas9 affects cell signaling, motility, and invasion in HGSC cells. LOC642852 is differentially expressed in HGSC cells at different anatomical sites. Its potential role in regulating the TLE3/miR-221-3p ceRNA network and FGFR3 merits further research.


Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2008 ◽  
Author(s):  
Priyanka Gokulnath ◽  
Tiziana de Cristofaro ◽  
Ichcha Manipur ◽  
Tina Di Palma ◽  
Amata Amy Soriano ◽  
...  

High-Grade Serous Ovarian Carcinoma (HGSC) is the most incidental and lethal subtype of epithelial ovarian cancer (EOC) with a high mortality rate of nearly 65%. Recent findings aimed at understanding the pathogenesis of HGSC have attributed its principal source as the Fallopian Tube (FT). To further comprehend the exact mechanism of carcinogenesis, which is still less known, we performed a transcriptome analysis comparing FT and HGSC. Our study aims at exploring new players involved in the development of HGSC from FT, along with their signaling network, and we chose to focus on non-coding RNAs. Non-coding RNAs (ncRNAs) are increasingly observed to be the major regulators of several cellular processes and could have key functions as biological markers, as well as even a therapeutic approach. The most physiologically relevant and significantly dysregulated non-coding RNAs were identified bioinformatically. After analyzing the trend in HGSC and other cancers, MAGI2-AS3 was observed to be an important player in EOC. We assessed its tumor-suppressive role in EOC by means of various assays. Further, we mapped its signaling pathway using its role as a miRNA sponge to predict the miRNAs binding to MAGI2AS3 and showed it experimentally. We conclude that MAGI2-AS3 acts as a tumor suppressor in EOC, specifically in HGSC by sponging miR-15-5p, miR-374a-5p and miR-374b-5p, and altering downstream signaling of certain mRNAs through a ceRNA network.


2017 ◽  
Vol 57 (2) ◽  
pp. 225-234 ◽  
Author(s):  
Shuo Chen ◽  
Li-li Wang ◽  
Kai-Xuan Sun ◽  
Yin-ling Xiu ◽  
Zhi-Hong Zong ◽  
...  

2020 ◽  
Vol 40 (12) ◽  
pp. 6677-6684
Author(s):  
NATALIE FILIPPOV-LEVY ◽  
BEN DAVIDSON ◽  
REUVEN REICH

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