A Novel lncRNA IHS Promotes Tumor Proliferation and Metastasis in HCC by Regulating the ERK- and AKT/GSK-3β-Signaling Pathways

Chen, Zheng; Yu, Wei; Zhou, Qiming; Zhang, Jianlong; Jiang, Hai; Hao, Dake; Wang, Jie; Zhou, Zhenyu; He, Chuanchao; Xiao, Zhiyu

doi:10.1016/j.omtn.2019.04.021

Cited by 46 publications

(38 citation statements)

References 47 publications

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“…Gene set enrichment analysis (GESA) showed that upregulation of Linc00839 in TCGA datasets might be related to different signaling pathways in cancer, the apoptosis pathway and the Jak‐STAT3 signaling pathway (Figure 6A). Recent studies have proven that the MAPK/AKT signaling pathway functions as a crucial regulator in cancer cell apoptosis and chemoresistant processes 28‐30 . Therefore, we assessed the activation status of the MAPK/AKT pathways regulated by Linc00839.…”

Section: Resultsmentioning

confidence: 99%

A nuclear lncRNA Linc00839 as a Myc target to promote breast cancer chemoresistance via PI3K/AKT signaling pathway

et al. 2020

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Chemoresistance has become a leading cause of mortality in breast cancer patients and is one of the major obstacles for improving the clinical outcome. Long noncoding RNAs play important roles in breast cancer tumorigenesis and chemoresistance. However, the involvement and regulation of lncRNAs in breast cancer chemoresistance are not completely understood. Here, we reported that Linc00839 was localized in the nucleus and upregulated in chemoresistant breast cancer cells and tissues, and high level of Linc00839 was associated with a poor prognosis. Knockdown of Linc00839 significantly suppressed proliferation, invasion, and migration, sensitized cells to paclitaxel in vitro and inhibited transplant tumor development in vivo. Mechanistically, we found that Myc could directly bind to the promoter region of Linc00839 and activate its transcription. Furthermore, Linc00839 overexpression increased the expression of Myc and the RNA‐binding protein Lin28B and activated the PI3K/AKT signaling pathway. We also discovered that Lin28B positively interacted with Linc00839 and was upregulated in breast cancer tissues. Taken together, for the first time, we showed that Linc00839 was activated by Myc and promoted proliferation and chemoresistance in breast cancer through binding with Lin28B. These findings provide new insight into the regulatory mechanism of Linc00839 and propose a Myc/Linc00839/Lin28B feedback loop that could be used as a novel therapeutic target for breast cancer.

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Section: Resultsmentioning

confidence: 99%

A nuclear lncRNA Linc00839 as a Myc target to promote breast cancer chemoresistance via PI3K/AKT signaling pathway

et al. 2020

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“…In addition, SMYD3 is over-expressed in HBx-induced HCC, and it promotes invasion and metastasis through transcriptional activation of a novel oncogenic lncRNA, lncIHC [79].…”

Section: Smyd3 Promotes Tumor Cell Migrationmentioning

confidence: 99%

SMYD3: An Oncogenic Driver Targeting Epigenetic Regulation and Signaling Pathways

Bottino

Peserico

Simone

et al. 2020

Cancers

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SMYD3 is a member of the SMYD lysine methylase family and plays an important role in the methylation of various histone and non-histone targets. Aberrant SMYD3 expression contributes to carcinogenesis and SMYD3 upregulation was proposed as a prognostic marker in various solid cancers. Here we summarize SMYD3-mediated regulatory mechanisms, which are implicated in the pathophysiology of cancer, as drivers of distinct oncogenic pathways. We describe SMYD3-dependent mechanisms affecting cancer progression, highlighting SMYD3 interplay with proteins and RNAs involved in the regulation of cancer cell proliferation, migration and invasion. We also address the effectiveness and mechanisms of action for the currently available SMYD3 inhibitors. The findings analyzed herein demonstrate that a complex network of SMYD3-mediated cytoplasmic and nuclear interactions promote oncogenesis across different cancer types. These evidences depict SMYD3 as a modulator of the transcriptional response and of key signaling pathways, orchestrating multiple oncogenic inputs and ultimately, promoting transcriptional reprogramming and tumor transformation. Further insights into the oncogenic role of SMYD3 and its targeting of different synergistic oncogenic signals may be beneficial for effective cancer treatment.

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“…Akt and ERK signaling pathways have been known as the regulators of cell growth in HCC. 20 As indicated in Figure 5A-F, overexpression of RP5-833A20.1 significantly upregulated the expressions of Bax, active caspase 3, and markedly downregulated the expressions of Bcl-2, p-Akt and p-ERK in Huh-7 cells. These data illustrated that overexpression of RP5-833A20.1 could induce the apoptosis of HCC cells via inhibiting Akt/ERK pathway.…”

Section: Overexpression Of Rp5-833a201 Induced Apoptosis Of Hcc Cellmentioning

confidence: 78%

<p>Long Noncoding RNA RP5-833A20.1 Suppresses Tumorigenesis In Hepatocellular Carcinoma Through Akt/ERK Pathway By Targeting miR-18a-5p</p>

Chen

Pan

et al. 2019

OTT

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Background: Previous studies indicated that long noncoding RNAs (lncRNAs) played vital roles in the development and progression of hepatocellular carcinoma (HCC). Recently, downregulation of lncRNA RP5-833A20.1 has been observed in HCC tissues. However, the underlying mechanism by which RP5-833A20.1 regulates the proliferation and apoptosis in HCC has not been investigated. Thus, this study aimed to investigate the role of RP5-833A20.1 in the progression of HCC. Methods: The levels of RP5-833A20.1 in 30 pairs of HCC tissues and adjacent normal tissues were detected by RT-qPCR. In addition, the effects of RP5-833A20.1 on cell proliferation, apoptosis and invasion were evaluated by CCK-8, flow cytometric, transwell assays, respectively. Meanwhile, the dual-luciferase reporter system assay was used to explore the interaction of RP5-833A20.1 and miR-18a-5p in HCC. Results: The level of RP5-833A20.1 was significantly downregulated in HCC tissues and HCC cell lines. Downregulation of RP5-833A20.1 markedly promoted the proliferation and invasion of Bel-7402 cells. In addition, overexpression of RP5-833A20.1 notably inhibited the proliferation and invasion of Huh7 cells. Moreover, overexpression of RP5-833A20.1 obviously induced the apoptosis of Huh7 cells via increasing the levels of Bax and active caspase 3, and decreasing the levels of Bcl-2, p-Akt and pERK. Meanwhile, in vivo experiments performed also indicated that overexpression of RP5-833A20.1 could inhibit the tumorigenesis of subcutaneous Huh7 xenograft in nude mice. Furthermore, bioinformatics and luciferase reporter assay identified that RP5-833A20.1 functioned as a competing endogenous RNA (ceRNA) for miR-18a-5p in HCC. Conclusion: In this study, we found that RP5-833A20.1 was downregulated in HCC tissues. In addition, RP5-833A20.1 could suppress the tumorigenesis in HCC through inhibiting Akt/ ERK pathway by acting as a ceRNA for miR-18a-5p. Therefore, RP5-833A20.1 might be a valuable and potential biomarker and therapeutic target for the treatment of HCC.

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A Novel lncRNA IHS Promotes Tumor Proliferation and Metastasis in HCC by Regulating the ERK- and AKT/GSK-3β-Signaling Pathways

Cited by 46 publications

References 47 publications

A nuclear lncRNA Linc00839 as a Myc target to promote breast cancer chemoresistance via PI3K/AKT signaling pathway

A nuclear lncRNA Linc00839 as a Myc target to promote breast cancer chemoresistance via PI3K/AKT signaling pathway

SMYD3: An Oncogenic Driver Targeting Epigenetic Regulation and Signaling Pathways

<p>Long Noncoding RNA RP5-833A20.1 Suppresses Tumorigenesis In Hepatocellular Carcinoma Through Akt/ERK Pathway By Targeting miR-18a-5p</p>

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