The Emerging Role of Long Non-Coding RNAs in the Metastasis of Hepatocellular Carcinoma

Chen, Xuejiao; Tang, Feng Ru; Arfuso, Frank; Cai, Wen-Qi; Ma, Zhaowu; Yang, Jiyuan; Sethi, Gautam

doi:10.3390/biom10010066

Cited by 72 publications

(41 citation statements)

References 86 publications

(104 reference statements)

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“…Accumulating evidence indicated that lncRNAs have the signi cant function in the carcinogenesis and the progression of malignancies during these years [23]. Therefore, it's crucial to investigate the regulatory characteristics of lncRNAs in the pathogenesis of HCC.…”

Section: Discussionmentioning

confidence: 99%

LncRNA ZFPM2-AS1 Promotes Metastasis and Epithelial-mesenchymal Transition of Hepatocellular Carcinoma via Targeting miR-3612/ADAM15 Axis

Yang¹,

Chen²,

Yao³

et al. 2020

Preprint

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Background: Long non-coding RNAs (lncRNAs) have obtained growing attention due to their potential effects as novel regulators in various tumors. This study aimed to investigate the expression and roles of lncRNA ZFPM2-AS1 in the progression of hepatocellular carcinoma (HCC). Methods: Transwell was used to determine migration and invasion of HCC cells in vitro. The lung metastasis mouse model was established to detect tumor metastasis of HCC in vivo. The direct binding of miR-3612 to 3'UTR of DAM15 was confirmed by luciferase reporter assay. The expression of ZFPM2-AS1 and miR-3612 in HCC specimens and cell lines were detected by real-time PCR. The correlation among ZFPM2-AS1 and miR-3612 were disclosed by a dual-luciferase reporter assay, RIP assay and biotin pull-down assay.Results: In present study, we found that ZFPM2-AS1 was up-regulated in HCC tissues and cells and its upregulation was associated with TNM stage, vascular invasion, and poor prognosis of HCC patients. Functionally, gain- and loss-of-function experiments indicated that ZFPM2-AS1 promoted cell migration, invasion and EMT progress in vitro and in vivo. ZFPM2-AS1 could function as a competing endogenous RNA (ceRNA) by sponging miR-3612 in HCC cells. Mechanically, miR-3612 inhibited HCC metastasis and alternation of miR-3612 reversed the promotive effects of ZFPM2-AS1 on HCC cells. In addition, we confirmed that ADAM15 was a direct target of miR-3612 in HCC and mediated the biological effects of miR-3612 and ZFPM2-AS1 in HCC. Curcumin, an active derivative from turmeric, exerts its anticancer effects through ZFPM2-AS1/miR-3612/ADAM15 pathway. Our data identified ZFPM2-AS1 as a novel oncogenic lncRNA and correlated malignant clinical outcomes in HCC patients. Conclusions: ZFPM2-AS1 performed as oncogenic role via targeting miR-3612 and subsequently promoted ADAM15 expression in HCC. Our results revealed that ZFPM2-AS1 could be a potential prognostic biomarker and therapeutic target for HCC.

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Section: Discussionmentioning

confidence: 99%

LncRNA ZFPM2-AS1 Promotes Metastasis and Epithelial-mesenchymal Transition of Hepatocellular Carcinoma via Targeting miR-3612/ADAM15 Axis

Yang¹,

Chen²,

Yao³

et al. 2020

Preprint

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“…The diverse regulatory functions of lncRNAs in various biological processes [ 19 , 20 ] control the expression of genes by different mechanisms [ 21 ]. These mechanisms include acting as decoys (molecular sinks for transcription factors and repressors to facilitate gene activation and silencing), guides (bind to enzymatically active or regulatory protein complexes and lead them to a specific target), scaffolds (act as a central platform to which various protein complexes can tether and lead to specific genomic locations), signaling molecules (associated with specific signaling pathways), and miRNA sponges (modulating miRNA expression) [ 22 ].…”

Section: Lncrnasmentioning

confidence: 99%

Mechanistic Involvement of Long Non-Coding RNAs in Oncotherapeutics Resistance in Triple-Negative Breast Cancer

Kansara

Pandey

Lobie

et al. 2020

Cells

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Triple-negative breast cancer (TNBC) is one of the most lethal forms of breast cancer (BC), with a significant disease burden worldwide. Chemoresistance and lack of targeted therapeutics are major hindrances to effective treatments in the clinic and are crucial causes of a worse prognosis and high rate of relapse/recurrence in patients diagnosed with TNBC. In the last decade, long non-coding RNAs (lncRNAs) have been found to perform a pivotal role in most cellular functions. The aberrant functional expression of lncRNAs plays an ever-increasing role in the progression of diverse malignancies, including TNBC. Therefore, lncRNAs have been recently studied as predictors and modifiers of chemoresistance. Our review discusses the potential involvement of lncRNAs in drug-resistant mechanisms commonly found in TNBC and highlights various therapeutic strategies to target lncRNAs in this malignancy.

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“…The invasion of cancer cells into surrounding tissues and vessels is an early stage of tumor metastasis. As more than 90% of cancer patients die due to persistent recurrence, metastasis and chemotherapy resistance, there is a need for studies to prevent or target metastasis [116][117][118][119][120][121][122]. Casticin significantly reduced the cell migration rate by 77.41% after 48 h of 5 µM compared to the control of DU145 cells [99] and inhibited cell migration by 93% after 24 h of 200 nM in human melanoma A375.S2 cancer cells [123].…”

Section: Effect Of Casticin On Metastasismentioning

confidence: 99%

An Overview of the Potential Antineoplastic Effects of Casticin

et al. 2020

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Cancer persists as one of the leading causes of deaths worldwide, contributing to approximately 9.6 million deaths per annum in recent years. Despite the numerous advancements in cancer treatment, there is still abundant scope to mitigate recurrence, adverse side effects and toxicities caused by existing pharmaceutical drugs. To achieve this, many phytochemicals from plants and natural products have been tested against cancer cell lines in vivo and in vitro. Likewise, casticin, a flavonoid extracted from the Vitex species, has been isolated from the leaves and seeds of V. trifolia and V. agnus-castus. Casticin possesses a wide range of therapeutic properties, including analgesic, anti-inflammatory, antiangiogenic, antiasthmatic and antineoplastic activities. Several studies have been conducted on the anticancer effects of casticin against cancers, including breast, bladder, oral, lung, leukemia and hepatocellular carcinomas. The compound inhibits invasion, migration and proliferation and induces apoptosis (casticin-induced, ROS-mediated and mitochondrial-dependent) and cell cycle arrest (G0/G1, G2/M, etc.) through different signaling pathways, namely the PI3K/Akt, NF-κB, STAT3 and FOXO3a/FoxM1 pathways. This review summarizes the chemo-preventive ability of casticin as an antineoplastic agent against several malignancies.

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The Emerging Role of Long Non-Coding RNAs in the Metastasis of Hepatocellular Carcinoma

Cited by 72 publications

References 86 publications

LncRNA ZFPM2-AS1 Promotes Metastasis and Epithelial-mesenchymal Transition of Hepatocellular Carcinoma via Targeting miR-3612/ADAM15 Axis

LncRNA ZFPM2-AS1 Promotes Metastasis and Epithelial-mesenchymal Transition of Hepatocellular Carcinoma via Targeting miR-3612/ADAM15 Axis

Mechanistic Involvement of Long Non-Coding RNAs in Oncotherapeutics Resistance in Triple-Negative Breast Cancer

An Overview of the Potential Antineoplastic Effects of Casticin

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