Long noncoding RNA MYLK-AS1 promotes growth and invasion of hepatocellular carcinoma through the EGFR/HER2-ERK1/2 signaling pathway

Chang

et al. 2020

J Exp Clin Cancer Res

Background Long non-coding RNAs (lncRNAs) are crucial in the invasion, angiogenesis, progression, and metastasis of hepatocellular carcinoma (HCC). The lncRNA MYLK-AS1 promotes the growth and invasion of HCC through the EGFR/HER2-ERK1/2 signaling pathway. However, the clinical significance of MYLK-AS1 in HCC still needs to be further determined. Methods Bioinformatic analysis was performed to determine the potential relationship among MYLK-AS1, miRNAs and mRNAs. A total of 156 samples of normal liver and paired HCC tissues from HCC patients were used to evaluate MYLK-AS1 expression by qRT-PCR. Human HCC cell lines were used to evaluate the colony formation, cell proliferation, migration, invasion, cell cycle and apoptosis after transfection of lentiviral short-hairpin RNAs (shRNAs) targeting MYLK-AS1 or MYLK-AS1 vectors. The competitive endogenous RNA (ceRNA) mechanism was clarified using fluorescence in situ hybridization (FISH), Western blotting, qPCR, RNA binding protein immunoprecipitation (RIP), and dual luciferase reporter analysis. Results MYLK-AS1 up-regulation was detected in the HCC tumor tissues and cell lines associated with the enhancement of the angiogenesis and tumor progression. The down-regulation of MYLK-AS1 reversed the effects on angiogenesis, proliferation, invasion and metastasis in the HCC cells and in vivo. MYLK-AS1 acted as ceRNA, capable of regulating the angiogenesis in HCC, while the microRNA miR-424-5p was the direct target of MYLK-AS1. Promoting the angiogenesis and the tumor proliferation, the complex MYLK-AS1/miR-424-5p activated the VEGFR-2 signaling through E2F7, whereas the specific targeting of E2F transcription factor 7 (E2F7) by miR-424-5p, was indicated by the mechanism studies. Conclusions MYLK-AS1 and E2F7 are closely related to some malignant clinicopathological features and prognosis of HCC, thus the MYLK-AS1/ miR-424-5p/E2F7 signaling pathway might represent a promising treatment strategy to combat HCC.

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

LncRNA MYLK-AS1 facilitates tumor progression and angiogenesis by targeting miR-424-5p/E2F7 axis and activating VEGFR-2 signaling pathway in hepatocellular carcinoma

Teng

Chang

et al. 2020

J Exp Clin Cancer Res

“…EGFR (epidermal growth factor receptor) and HER2, members of the EGFR family, play critical roles in sustaining cancer cell proliferation, aided by the downstream ERK1/2 signaling pathway. In hepatocellular carcinoma, the NAT MYLK-AS1 can increase EGFR and HER2 expression and subsequently trigger the ERK1/2 signaling pathway, leading to increased cancer cell proliferation [ 105 ].…”

Section: Introductionmentioning

confidence: 99%

Natural antisense transcripts in the biological hallmarks of cancer: powerful regulators hidden in the dark

Zhao

Chen

et al. 2020

J Exp Clin Cancer Res

Natural antisense transcripts (NATs), which are transcribed from opposite strands of DNA with partial or complete overlap, affect multiple stages of gene expression, from epigenetic to post-translational modifications. NATs are dysregulated in various types of cancer, and an increasing number of studies focusing on NATs as pivotal regulators of the hallmarks of cancer and as promising candidates for cancer therapy are just beginning to unravel the mystery. Here, we summarize the existing knowledge on NATs to highlight their underlying mechanisms of functions in cancer biology, discuss their potential roles in therapeutic application, and explore future research directions.

“…The presence of dysregulated lncRNA expression was recently noticed in gastrointestinal cancers and HCC (26). It was also previously demonstrated that MYLK-AS1 promotes the growth of the HCC and invasion through the EGFR/HER2-ERK1/2 signaling pathway (7). Besides, MYLK-AS1 association with the transcription factor MYLK was known to contribute to the HCC progression by regulating the cytoskeleton to enhance the epithelial-mesenchymal transition (27).…”

Section: Discussionmentioning

confidence: 94%

“…Recently, an overall survival (OS) risk scoring system for HCC patients has been constructed based on the expression of 6 lncRNAs including MYLK-AS1 (6). According to reports, MYLK-AS1 promotes the growth and invasion of HCC through the EGFR/HER2-ERK1/2 signaling pathway (7). In addition, MYLK-AS1 is down-regulated in colon adenocarcinoma compared with paired adjacent normal tissues (8).…”

Section: Introductionmentioning

confidence: 99%

LncRNA MYLK-AS1 facilitates tumor progression and angiogenesis by targeting miR-424-5p/E2F7 axis and activating VEGFR-2 signaling pathway in hepatocellular carcinoma

Teng

Chang

et al. 2020

Preprint

Background: Long non-coding RNAs (lncRNAs) are crucial in the invasion, angiogenesis, progression, and metastasis of hepatocellular carcinoma (HCC). The lncRNA MYLK-AS1 promotes the growth and invasion of HCC through the EGFR/HER2-ERK1/2 signaling pathway. However, the clinical significance of MYLK-AS1 in HCC still needs to be further determined.Methods: Bioinformatic analysis was performed to determine the potential relationship among MYLK-AS1, miRNAs and mRNAs. A total of 156 samples of normal liver and paired HCC tissues from HCC patients were used to evaluate MYLK-AS1 expression by qRT-PCR. Human HCC cell lines were used to evaluate the colony formation, cell proliferation, migration, invasion, cell cycle and apoptosis after transfection of lentiviral short-hairpin RNAs (shRNAs) targeting MYLK-AS1 or MYLK-AS1 vectors. The competitive endogenous RNA (ceRNA) mechanism was clarified using fluorescence in situ hybridization (FISH), Western blotting, qPCR, RNA binding protein immunoprecipitation (RIP), and dual luciferase reporter analysis.Results: MYLK-AS1 up-regulation was detected in the HCC tumor tissues and cell lines associated with the enhancement of the angiogenesis and tumor progression. The down-regulation of MYLK-AS1 reversed the effects on angiogenesis, proliferation, invasion and metastasis in the HCC cells and in vivo. MYLK-AS1 acted as ceRNA, capable of regulating the angiogenesis in HCC, while the microRNA miR-424-5p was the direct target of MYLK-AS1. Promoting the angiogenesis and the tumor proliferation, the complex MYLK-AS1/miR-424-5p activated the VEGFR2 signaling through E2F7, whereas the specific targeting of E2F transcription factor 7 (E2F7) by miR-424-5p, was indicated by the mechanism studies.Conclusions: MYLK-AS1 and E2F7 are closely related to some malignant clinicopathological features and prognosis of HCC, thus the MYLK-AS1/ miR-424-5p/E2F7 signaling pathway might represent a promising treatment strategy to combat HCC.