LINC00460 promotes hepatocellular carcinoma development through sponging miR-485-5p to up-regulate PAK1

Tu, Jianfei; Zhao, Zhongwei; Xu, Min; Chen, Minjiang; Weng, Qiaoyou; Ji, Jiansong

doi:10.1016/j.biopha.2019.109213

Cited by 40 publications

(47 citation statements)

References 30 publications

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“…12 LINC00460 could promote HCC progression through sponging miR-485-5p to elevate PAK1. 17 Besides, miR-342-3p has been served as a tumor suppressor in HCC tumorigenesis, and its low expression is associated with poor prognosis of HCC. 18 Moreover, LINC00460 was found to promote gastric cancer cell proliferation, migration and invasion by sponging miR-342-3p to up-regulate KDM2A expression in GC cells.…”

Section: Discussionmentioning

confidence: 99%

<p>Long Noncoding RNA LINC00460 Promotes Hepatocellular Carcinoma Progression via Regulation of miR-342-3p/AGR2 Axis</p>

Yang¹,

Li²,

Chen³

et al. 2020

OTT

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Background: Hepatocellular carcinoma (HCC) is the leading cause of cancer-related death worldwide. LINC00460, a novel long non-coding RNA (lncRNA), was recently confirmed as an oncogene in various cancers. However, the biological function and underlying mechanism of LINC00460 in HCC is largely obscure. Methods: Fifty pairs of tumor tissue and adjacent normal tissues from HCC patients, as well as six HCC cell lines and a normal human hepatic epithelial cell line were subjected to qRT-PCR assay to evaluate the expression levels of LINC00460. CCK-8 assays were used to detect the proliferation of HCC cells. Transwell assay was used to measure the migration and invasion abilities of HCC cells. RNA pull-down and luciferase assays were performed to verify the direct interaction between LINC00460 and miR-342-3p. A xenograft model of HCC was established to validate the in vivo function of LINC00460 in HCC progression. Results: We firstly detected LINC00460 expression was significantly upregulated in both HCC tumor tissues and cell lines. The upregulation of LINC00460 was positively associated with HCC progression. Functionally, LINC00460 facilitated HCC cell proliferation, migration, and invasion capacities, which due to that LINC00460 could physically bind to and repress miR-342-3p to elevate the expression of AGR2. Conclusion: Our data firstly reveal the clinical relevance, biological function, and regulatory mechanism of LINC00460 in HCC development. LINC00460 promotes HCC progression by elevating AGR2 expression via sponging miR-342-3p, providing a promising therapeutic target for HCC treatment.

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Section: Discussionmentioning

confidence: 99%

<p>Long Noncoding RNA LINC00460 Promotes Hepatocellular Carcinoma Progression via Regulation of miR-342-3p/AGR2 Axis</p>

Yang¹,

Li²,

Chen³

et al. 2020

OTT

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“…In addition, knockdown of LINC00460 and LINC00488 induced cell apoptosis and reduced angiogenesis via downregulation of PAK1 and TLN1, respectively, which are direct targets of miR-485-5p and miR-330-5p. LINC00460 and LINC00488 sponged miR-485-5p and miR-330-5p leading to HCC tumorigenesis and angiogenesis, respectively [69,70].…”

Section: Long Non-coding Rna and Microrna Network In Hccmentioning

confidence: 99%

Epigenetic Associations between lncRNA/circRNA and miRNA in Hepatocellular Carcinoma

Han

Hur

Cho

et al. 2020

Cancers

121

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The three major members of non-coding RNAs (ncRNAs), named microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), play an important role in hepatocellular carcinoma (HCC) development. Recently, the competing endogenous RNA (ceRNA) regulation model described lncRNA/circRNA as a sponge for miRNAs to indirectly regulate miRNA downstream target genes. Accumulating evidence has indicated that ceRNA regulatory networks are associated with biological processes in HCC, including cancer cell growth, epithelial to mesenchymal transition (EMT), metastasis, and chemoresistance. In this review, we summarize recent discoveries, which are specific ceRNA regulatory networks (lncRNA/circRNA-miRNA-mRNA) in HCC and discuss their clinical significance.

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“…The regulation of miRNAs on target genes is also a hot spot in oncology. Studies have revealed that miR-485-5p 79 , miR-140-5p 80 , miR-96 81 , miR-7 82 , miR-494 83 , miR-34b 84 , and miR-145 85 can directly target and degrade the mRNA of PAK1 in order to block the translation of PAK1. In addition, PAK1 can be directly activated by interaction with Rho-related GTPases CDC42 and RAC1 86 .…”

Section: Endogenous Upstream Regulators Of Pak1mentioning

confidence: 99%

“…For instance, LncRNA-H19 suppresses miR-15b expression to activate the CDC42-PAK1 pathway 90 . LINC00460 promotes tumor progression through sponging miR-485-5p and up-regulating PAK1 79 , and MALAT1 interacts with miR-140-5p to abolish the inhibition of PAK1 80 ( Figure 3 A ). In addition, transcriptional modification by transcription factor is another major regulation of PAK1.…”

Section: Endogenous Upstream Regulators Of Pak1mentioning

confidence: 99%

P21-Activated Kinase 1: Emerging biological functions and potential therapeutic targets in Cancer

Yao

Rajoka

et al. 2020

Theranostics

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The p21-Activated kinase 1 (PAK1), a member of serine-threonine kinases family, was initially identified as an interactor of the Rho GTPases RAC1 and CDC42, which affect a wide range of processes associated with cell motility, survival, metabolism, cell cycle, proliferation, transformation, stress, inflammation, and gene expression. Recently, the PAK1 has emerged as a potential therapeutic target in cancer due to its role in many oncogenic signaling pathways. Many PAK1 inhibitors have been developed as potential preclinical agents for cancer therapy. Here, we provide an overview of essential roles that PAK1 plays in cancer, including its structure and autoactivation mechanism, its crucial function from onset to progression to metastasis, metabolism, immune escape and even drug resistance in cancer; endogenous regulators; and cancer-related pathways. We also summarize the reported PAK1 small-molecule inhibitors based on their structure types and their potential application in cancer. In addition, we provide overviews on current progress and future challenges of PAK1 in cancer, hoping to provide new ideas for the diagnosis and treatment of cancer.

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LINC00460 promotes hepatocellular carcinoma development through sponging miR-485-5p to up-regulate PAK1

Cited by 40 publications

References 30 publications

<p>Long Noncoding RNA LINC00460 Promotes Hepatocellular Carcinoma Progression via Regulation of miR-342-3p/AGR2 Axis</p>

<p>Long Noncoding RNA LINC00460 Promotes Hepatocellular Carcinoma Progression via Regulation of miR-342-3p/AGR2 Axis</p>

Epigenetic Associations between lncRNA/circRNA and miRNA in Hepatocellular Carcinoma

P21-Activated Kinase 1: Emerging biological functions and potential therapeutic targets in Cancer

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