LncRNA-HGBC stabilized by HuR promotes gallbladder cancer progression by regulating miR-502-3p/SET/AKT axis

Hu, Yunping; Jin, Yunpeng; Wu, Xiangsong; Yang, Yang; Li, Yongsheng; Li, Huaifeng; Xiang, Sheng; Song, Xiaoling; Jiang, Lin; Zhang, Yi-Jian; Huang, Wen; Chen, Shi-li; Liu, Fa-Tao; Chen, Chen; Zhu, Qin; Chen, Hongzhuan; Shao, Rong; Liu, Yingbin

doi:10.1186/s12943-019-1097-9

Cited by 139 publications

(101 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A similar scenario was discovered for HuR and lncRNA-HGBC (lncRNA highly expressed in gallbladder carcinoma) by Hu and colleagues [56]. LncRNA-HGBC was first identified in a microarray-based analysis to be highly upregulated in gallbladder cancer tissue from nine patients and was then shown to be linked to gallbladder cancer proliferation and invasion in vitro as well as in vivo [56,83].…”

Section: Human Antigen R (Hur)mentioning

confidence: 56%

“…Stabilization by shielding from RNA decay-promoting proteins [55] lncRNA-HGBC Stabilization by shielding from RNA decay-promoting proteins [56] lncRNA-p21 Promotion of degradation by recruitment of let7-Ago2 [57] HOTAIR Promotion of degradation by recruitment of let7-Ago2 [58] RMRP Facilitation of nuclear export via interaction with CRM1 [59] Serine/arginine-rich splicing factor 1 (SRSF1) NEAT1 Stabilization by an unknown mechanism [60] Arginine/uridine-rich RNA element (ARE)/poly(U)-binding/degradation factor 1 (AUF1) NEAT1 Destabilization, probably by recruitment of a deadenylase complex [61] Polyadenylate-binding protein 1 (PABPN1) NEAT1 Promotion of degradation by recruitment of NEXT-exosome [62,63] TUG1 Promotion of degradation by recruitment of NEXT-exosome [62,63] Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) HULC Promotion of degradation by recruitment of the deadenylase complex CCR4-NOT via CNOT1 [64] H19 Targeting of lamellipodia and perinuclear regions [65] Tristetraprolin (TTP) HOTAIR Promotion of degradation, most likely by recruitment of the deadenylase complex CCR4-NOT [66,67] G-rich RNA sequence-binding factor 1 (GRSF1) RMRP Retention in the mitochondrial matrix by an unknown mechanism [68] Heterogeneous nuclear ribonucleoprotein K (hnRNPK) MALAT1 Retention in the nucleus by an unknown mechanism [69,70]…”

Section: Neat1mentioning

confidence: 99%

“…HuR is frequently upregulated in cancer cells and is known to be involved in many hallmarks of cancer, such as invasion, angiogenesis, and inflammation, by post-transcriptionally regulating various cancer-related mRNAs [71,72,[74][75][76]. HuR not only binds to protein-coding mRNA but also interacts with lncRNAs, thereby influencing their stability both in a positive and negative manner [55][56][57][58]77].…”

Section: Human Antigen R (Hur)mentioning

confidence: 99%

“…LncRNA-HGBC was first identified in a microarray-based analysis to be highly upregulated in gallbladder cancer tissue from nine patients and was then shown to be linked to gallbladder cancer proliferation and invasion in vitro as well as in vivo [56,83]. Using an RNA pulldown assay, where the in vitro transcribed biotin-labeled lncRNA-HGBC was incubated with lysate from a gallbladder cancer cell line and pulled down with streptavidin beads followed by mass spectrometry analysis of the associated proteins, HuR was identified as an interaction partner of lncRNA-HGBC [56]. This interaction was further verified with an RIP assay [56].…”

Section: Human Antigen R (Hur)mentioning

confidence: 99%

“…Using an RNA pulldown assay, where the in vitro transcribed biotin-labeled lncRNA-HGBC was incubated with lysate from a gallbladder cancer cell line and pulled down with streptavidin beads followed by mass spectrometry analysis of the associated proteins, HuR was identified as an interaction partner of lncRNA-HGBC [56]. This interaction was further verified with an RIP assay [56]. Using different fragments of the lncRNA, the authors were able to pinpoint the binding site to a region containing an ARE [56].…”

Section: Human Antigen R (Hur)mentioning

confidence: 99%

See 4 more Smart Citations

RNA-Binding Proteins as Important Regulators of Long Non-Coding RNAs in Cancer

Jonas

Calin

Pichler

2020

IJMS

102

View full text Add to dashboard Cite

The majority of the genome is transcribed into pieces of non-(protein) coding RNA, among which long non-coding RNAs (lncRNAs) constitute a large group of particularly versatile molecules that govern basic cellular processes including transcription, splicing, RNA stability, and translation. The frequent deregulation of numerous lncRNAs in cancer is known to contribute to virtually all hallmarks of cancer. An important regulatory mechanism of lncRNAs is the post-transcriptional regulation mediated by RNA-binding proteins (RBPs). So far, however, only a small number of known cancer-associated lncRNAs have been found to be regulated by the interaction with RBPs like human antigen R (HuR), ARE/poly(U)-binding/degradation factor 1 (AUF1), insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), and tristetraprolin (TTP). These RBPs regulate, by various means, two aspects in particular, namely the stability and the localization of lncRNAs. Importantly, these RBPs themselves are commonly deregulated in cancer and might thus play a major role in the deregulation of cancer-related lncRNAs. There are, however, still many open questions, for example regarding the context specificity of these regulatory mechanisms that, in part, is based on the synergistic or competitive interaction between different RBPs. There is also a lack of knowledge on how RBPs facilitate the transport of lncRNAs between different cellular compartments. Compared to protein-coding genes, lncRNAs are poorly conserved between different species and their expression levels are rather low [7,8]. Initially, this led to the belief that they were nothing but transcriptional noise [6][7][8]. Soon, however, it was discovered that lncRNAs do exhibit considerable functionality, for example as regulators of transcription [6][7][8]. Mechanisms of transcriptional regulation by lncRNAs are multifarious and can occur either in cis or in trans, meaning either closer to or further away from the lncRNA's site of transcription, respectively [6,7]. A frequent mechanism of transcriptional regulation via lncRNAs is the recruitment, or prevention of such, of components of chromatin or histone-modifying complexes, like polycomb repressive complexes or histone deacetylase complexes [11][12][13]. LncRNAs can also direct transcription factors or cofactors to promoter regions of genes and facilitate the formation of chromatin loops between distant enhancers and promoters, as observed for some eRNAs [9,[14][15][16][17]. Another way that they can impact transcription is by interfering with the RNA polymerase II transcription machinery, thereby blocking transcriptional initiation or elongation [18]. LncRNAs are important regulators not only at the level of transcription but also at the post-transcriptional level [6,7]. They regulate pre-mRNA splicing by interacting with splicing factors or with the mRNA itself [19][20][21][22]. A well-studied example for this is metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), an lncRNA that interacts with serine/arginine (SR) spl...

show abstract

Section: Human Antigen R (Hur)mentioning

confidence: 56%

Section: Neat1mentioning

confidence: 99%

Section: Human Antigen R (Hur)mentioning

confidence: 99%

Section: Human Antigen R (Hur)mentioning

confidence: 99%

Section: Human Antigen R (Hur)mentioning

confidence: 99%

See 3 more Smart Citations

RNA-Binding Proteins as Important Regulators of Long Non-Coding RNAs in Cancer

Jonas

Calin

Pichler

2020

IJMS

102

View full text Add to dashboard Cite

show abstract

STAT3 activates the transcription of lncRNA NR2F1‐AS1 to promote the progression of melanoma via regulating the miR‐493‐5p/GOLM1 axis

Bai

Huang

et al. 2021

The Journal of Gene Medicine

View full text Add to dashboard Cite

BackgroundLong non‐coding RNAs (lncRNAs) are vital regulators during the biological processes of melanoma. The present study aimed to uncover biological functions of lncRNA termed NR2F1 antisense RNA 1 (NR2F1‐AS1) in melanoma and the potential mechanisms.MethodsRelative levels of NR2F1‐AS1 and miR‐493‐5p in a total of 137 paired primary melanoma tissues and corresponding non‐tumor tissues, as well as three melanoma cell lines, were examined by a real‐time polymerase chain reaction. The clinical significance of NR2F1‐AS1 expression was analyzed statistically. The STAT3 binding motif in the promoter region of NR2F1‐AS1 was identified by JASPAR (http://jaspar.genereg.net). The association between STAT3 and NR2F1‐AS1 was determined by dual‐luciferase reporter and chromatin immunoprecipitation assays. The effects of NR2F1‐AS1 on cell proliferation, migration and were measured by cell counting kit‐8 (CCK‐8), Edu, transwell and wound healing assays. Dual‐luciferase reporter and RNA pull‐down assays were applied to validate the interaction among NR2F1‐AS1, miR‐493‐5p and GOLM1. Furthermore, in vivo experiments were conducted to demonstrate the oncogenic role of NR2F1‐AS1 in melanoma.ResultsUp‐regulated NR2F1‐AS1 and down‐regulated miR‐493‐5p were detected in melanoma tumors and cells. The overexpression of NR2F1‐AS1 was induced by STAT3. High NR2F1‐AS1 expression was correlated to advanced tumor stage and poor prognosis of melanoma. Functional studies using CCK‐8, Edu, transwell and wound healing assays revealed that the proliferative, migratory and invasive capacities of melanoma cells were attenuated by the by inhibition of NR2F1‐AS1. Moreover, NR2F1‐AS1 was able to up‐regulate GOLM1 through recognizing and binding miR‐493‐5p. Furthermore, knockdown of miR‐493‐5p distinctly reversed these inhibitory effects of NR2F1‐AS1 down‐regulation on the tumorigenesis and progression of melanoma.ConclusionsOur findings demonstrate a key role for NR2F1‐AS1 in melanoma progression via targeting miR‐493‐5p/GOLM1 axis.

show abstract

Inhibition of the long non‐coding RNA UNC5B‐AS1/miR‐4455/RSPO4 axis reduces cervical cancer growth in vitro and in vivo

Zhang

Wang

et al. 2021

The Journal of Gene Medicine

View full text Add to dashboard Cite

Background: Long non-coding RNAs (lncRNAs) are significant regulatory factors for the initiation and development of numerous malignant tumors, including cervical cancer (CC). The expression of lncRNA unc-5 netrin receptor B antisense RNA 1 (UNC5B-AS1, also known as UASR1) is up-regulated in tissues of cervical squamous cell carcinoma and endocervical adenocarcinoma compared to in normal tissues based on the GEPIA database. In the present study, we explored the functions of UNC5B-AS1 and its underlying mechanism with respect to CC development. Methods: A real-time quantitative polymerase chain reaction was applied for the detection of UNC5B-AS1 expression in CC cells. Cell counting kit-8, colony formation and transwell assays, as well as western blot and flow cytometry analyses, were employed to detect the biological effects of UNC5B-AS1 knockdown on malignant phenotypes of CC cells in vitro. In addition, the combination between microRNA-4455 (miR-4455) and UNC5B-AS1 or R-spondin 4 (RSPO4) was explored by RNA immunoprecipitation, luciferase reporter and RNA pulldown assays. A tumor xenograft nude mice model was established to explore the effect of UNC5B-AS1 depletion or miR-4455 overexpression on tumor growth. Results: UNC5B-AS1 is up-regulated in CC tissues and cells. The knockdown of UNC5B-AS1 inhibits CC cell proliferation, migration and invasion and promotes CC cell apoptosis. Mechanistically, UNC5B-AS1 binds with miR-4455 to up-regulate RSPO4 expression. RSPO4 is targeted by miR-4455 and its expression is negatively regulated by miR-4455 expression. In vivo assays revealed that UNC5B-AS1 depletion or miR-4455 overexpression inhibits tumor growth by regulating RSPO4 expression. Conclusions: Inhibition of UNC5B-AS1/miR-4455/RSPO4 reduces CC growth both in vitro and in vivo, furnishing new insights into molecular studies on UNC5B-AS1 with respect to CC development.

show abstract

LncRNA-HGBC stabilized by HuR promotes gallbladder cancer progression by regulating miR-502-3p/SET/AKT axis

Cited by 139 publications

References 48 publications

RNA-Binding Proteins as Important Regulators of Long Non-Coding RNAs in Cancer

RNA-Binding Proteins as Important Regulators of Long Non-Coding RNAs in Cancer

STAT3 activates the transcription of lncRNA NR2F1‐AS1 to promote the progression of melanoma via regulating the miR‐493‐5p/GOLM1 axis

Inhibition of the long non‐coding RNA UNC5B‐AS1/miR‐4455/RSPO4 axis reduces cervical cancer growth in vitro and in vivo

Contact Info

Product

Resources

About