LINC01413/hnRNP-K/ZEB1 Axis Accelerates Cell Proliferation and EMT in Colorectal Cancer via Inducing YAP1/TAZ1 Translocation

Ji, Lele; Li, Xiang; Zhou, Zhenhua; Zheng, Zhenlin; Jin, Li; Jiang, Fan

doi:10.1016/j.omtn.2019.11.027

Cited by 32 publications

(23 citation statements)

References 52 publications

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“…LncRNAs usually regulate target genes by interacting with RNA-binding proteins (RBPs). An increasing number of studies have identified the important roles of RBPs in regulating the lncRNAs and their downstream target genes [ 24 , 45 – 49 ]. We have identified hnRNPA1 as an interacting partner of H19 using RNA pull down and RIP assays.…”

Section: Discussionmentioning

confidence: 99%

LncRNAH19 improves insulin resistance in skeletal muscle by regulating heterogeneous nuclear ribonucleoprotein A1

Gui

Zhu

et al. 2020

Cell Commun Signal

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Background Skeletal muscle is essential for glucose and lipid metabolism. Growing evidence reveals the importance of long non-coding RNAs (LncRNAs) in metabolism. This study aimed to investigate the function of LncRNA H19 (H19) in lipid metabolism of skeletal muscle and its potential mechanisms. Methods Glucose tolerance, serum insulin and lipid content in serum and skeletal muscle were determined in control and H19-overexpressed db/db mice. Lipid metabolism was evaluated in H19-overexpressed or H19-silencing muscle cells by detecting lipid contents and mitochondria related functions. The underlying mechanisms were explored by RNA pull-down, mass spectrometry and RNA immunoprecipitation (RIP). Results H19 was downregulated in skeletal muscle of db/db mice. H19 overexpression in db/db mice inhibited lipid ectopic deposition in skeletal muscle, meanwhile improved glucose intolerance and insulin resistance as compared with control db/db mice treated with ad-GFP. Furthermore, overexpression of H19 reversed FFA-induced lipid accumulation and increased cellular respiration in muscle cells, while H19 knockdown exhibited opposite effects in muscle cells. Mechanistically, H19 interacted with heterogeneous nuclear ribonucleoprotein (hnRNPA1) which was validated by RNA pulldown and RIP analysis, which increased translation of fatty acid oxidation closely related genes PGC1a and CPT1b. Conclusion Our data suggest that overexpression of H19 ameliorates insulin resistance by reducing ectopic lipid accumulation in skeletal muscle. The possible underlying mechanisms are that overexpression of lncRNAH19 promotes fatty acids oxidation via targeting of hnRNPA1.

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Section: Discussionmentioning

confidence: 99%

LncRNAH19 improves insulin resistance in skeletal muscle by regulating heterogeneous nuclear ribonucleoprotein A1

Gui

Zhu

et al. 2020

Cell Commun Signal

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show abstract

“…LncRNAs usually regulate target genes by interacting with RNA-binding proteins (RBPs). An increasing number of studies have identi ed the important roles of RBPs in regulating the lncRNAs and their downstream target genes (24,(45)(46)(47)(48)(49). We have identi ed hnRNPA1 as an interacting partner of H19 using RNA pull down and RIP assays.…”

Section: Discussionmentioning

confidence: 99%

LncRNAH19 improves insulin resistance in skeletal muscle by regulating heterogeneous nuclear ribonucleoprotein A1

Gui

Zhu

Yi-Yi

et al. 2020

Preprint

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Background：Skeletal muscle is essential for glucose and lipid metabolism. Growing evidence reveals the importance of long non-coding RNAs (LncRNAs) in metabolism. This study aimed to investigate the function of LncRNA H19 (H19) in lipid metabolism of skeletal muscle and its potential mechanisms.Methods: Glucose tolerance, serum insulin and lipid content in serum and skeletal muscle were determined in control and H19-overexpressed db/db mice. Lipid metabolism was evaluated in H19-overexpressed or H19-silencing muscle cells by detecting lipid contents and mitochondria related functions. The underlying mechanisms were explored by RNA pull-down, mass spectrometry and RNA immunoprecipitation (RIP). Results: H19 was downregulated in skeletal muscle of db/db mice. H19 overexpression in db/db mice inhibited lipid ectopic deposition in skeletal muscle, meanwhile improved glucose intolerance and insulin resistance as compared with control db/db mice treated with ad-GFP. Furthermore, overexpression of H19 reversed FFA-induced lipid accumulation and increased cellular respiration in muscle cells, while H19 knockdown exhibited opposite effects in muscle cells. Mechanistically, H19 interacted with heterogeneous nuclear ribonucleoprotein (hnRNPA1) which was validated by RNA pulldown and RIP analysis, which increased translation of fatty acid oxidation closely related genes PGC1a and CPT1b. Conclusion: Our data suggest that overexpression of H19 ameliorates insulin resistance by reducing ectopic lipid accumulation in skeletal muscle. The possible underlying mechanisms are that overexpression of lncRNAH19 promotes fatty acids oxidation via targeting of hnRNPA1.

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“…c-Myc upregulated lncRNA (MYU) in colorectal cancer (CRC), was reported to directly interact with hnRNPK to stabilize the expression of cyclin-dependent kinase 6 (CDK6) (19). Several lncRNAs associated with hnRNPK including cancer susceptibility candidate 11 (CASC11) and Ets-1 promoter-associated noncoding RNA (pancEts-1) were reported to activate the Wnt pathway by stabilizing or activating b-catenin (20)(21)(22). Interaction of hnRNPK with LINC01413 increases the expression of ZEB1 by inducing the nuclear translocation of YAP1/TAZ1 (22).…”

Section: Discussionmentioning

confidence: 99%

hnRNPK-regulated LINC00263 promotes malignant phenotypes through miR-147a/CAPN2

Lee

Shin

et al. 2020

Preprint

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Background: Malignant characteristics of cancers, represented by rapid cell proliferation and high metastatic potential, are a major cause of high cancer-related mortality. As a multifunctional RNA-binding protein, heterogeneous nuclear ribonucleoprotein K (hnRNPK) is closely associated with cancer progression in various types of cancers. In this study, we sought to identify hnRNPK-regulated long intergenic non-coding RNAs (lincRNAs) that play a critical role in the regulation of cancer malignancy.Methods: Malignant phenotypes including metastatic and proliferative potential were examined using Transwell invasion assay, cell counting, and colony forming assay. To search for hnRNPK-regulated lincRNAs, RNA sequencing was performed. Using small RNA sequencing followed by antisense oligonucleotide pull-down, lincRNA-associated miRNAs were selected. The association between miRNA and target mRNA was determined by Argonaute 2-immunoprecipitation and luciferase reporter assay. Results: We found that hnRNPK controlled malignant phenotypes including invasiveness, proliferation, and clonogenicity. RNA sequencing and functional studies revealed that LINC00263, a novel target of hnRNPK, is involved in the oncogenic functions of hnRNPK. Knockdown of LINC00263 mitigated the malignant capabilities. Conversely, increased malignant phenotypes were observed in LINC00263-overexpressing cells. We also found that miR-147a negatively regulates LINC00263 via direct interaction, thus suppressing malignant capabilities. Moreover, knockdown of hnRNPK and LINC00263 upregulated miR-147a, indicating that LINC00263 serves as a ceRNA for miR-147a. By analyzing RNA sequencing data and miRNA target prediction, calpain 2 (CAPN2) was identified as a putative target of miR-147a. Ago2-IP and luciferase reporter assay revealed that miR-147a suppressed CAPN2 expression by directly binding to the 3'UTR of CAPN2 mRNA. Additionally, we found that the weakened malignant capabilities following knockdown of hnRNPK or LINC00263 were restored by miR-147a inhibition or CAPN2 overexpression.Conclusions: Our findings demonstrate that hnRNPK-regulated LINC00263 plays an important role in cancer malignancy by acting as a miR-147a decoy and thus upregulating CAPN2.

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LINC01413/hnRNP-K/ZEB1 Axis Accelerates Cell Proliferation and EMT in Colorectal Cancer via Inducing YAP1/TAZ1 Translocation

Cited by 32 publications

References 52 publications

LncRNAH19 improves insulin resistance in skeletal muscle by regulating heterogeneous nuclear ribonucleoprotein A1

LncRNAH19 improves insulin resistance in skeletal muscle by regulating heterogeneous nuclear ribonucleoprotein A1

LncRNAH19 improves insulin resistance in skeletal muscle by regulating heterogeneous nuclear ribonucleoprotein A1

hnRNPK-regulated LINC00263 promotes malignant phenotypes through miR-147a/CAPN2

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