Long noncoding RNA HULC accelerates the growth of human liver cancer stem cells by upregulating CyclinD1 through miR675-PKM2 pathway via autophagy

Wang, Chen; Jiang, Xiaoxue; Li, Xiaonan; Song, Shuting; Meng, Qiuyu; Wang, Liyan; Lu, Yanan; Xin, Xiaoru; Hu, Pu; Gui, Xin; Li, Tianming; Lu, Dongdong

doi:10.1186/s13287-019-1528-y

Cited by 33 publications

(30 citation statements)

References 55 publications

(52 reference statements)

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“…= 71), and as part of the core RS. HULC is a long non-coding RNA that has been identified as a driver of tumorigenesis in multiple cancers [37,38,39], including liver cancer, osteosarcoma, cervical cancer, pancreatic, stomach and ovarian cancers [40,41,42,43,44,45]. HULC expression is a predictor of poor prognosis across multiple cancers [46,47,48,49], and HULC silencing enhanced the effectiveness of chemotherapy in stomach cancer cell lines [44].…”

Section: Novel Melanoma Combinations Detected By Crsomentioning

confidence: 99%

Identifying Modules of Cooperating Cancer Drivers

Klein

Cannataro

Townsend

et al. 2020

Preprint

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AbstractIdentifying cooperating modules of driver alterations can provide biological insights to cancer causation and would advance the development of effective personalized treatments. We present Cancer Rule-Set Optimization (CRSO) for inferring the combinations of alterations that cooperate to drive tumor formation in individual patients. Application to 19 TCGA cancer types found a mean of 11 core driver combinations per cancer, comprising 2-6 alterations per combination, and accounting for a mean of 70% of samples per cancer. CRSO departs from methods based on statistical cooccurrence, which we demonstrate is a suboptimal criterion for investigating driver cooperation. CRSO identified well-studied driver combinations that were not detected by other approaches and nominated novel combinations that correlate with clinical outcomes in multiple cancer types. Novel synergies were identified in NRAS-mutant melanomas that may be therapeutically relevant. Core driver combinations involving NFE2L2 mutations were identified in four cancer types, supporting the therapeutic potential of NRF2 pathway inhibition. CRSO is available at https://github.com/mikekleinsgit/CRSO/.

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Section: Novel Melanoma Combinations Detected By Crsomentioning

confidence: 99%

Identifying Modules of Cooperating Cancer Drivers

Klein

Cannataro

Townsend

et al. 2020

Preprint

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“…IGF2BP1 presents an exception of an m6A-binding RBP with a documented effect on a cancer-associated lncRNA, namely the~500-nt-long lncRNA highly up-regulated in liver cancer (HULC) [64]. HULC, as described by its name, is "highly up-regulated in liver cancer" and contributes to carcinogenesis, not only in the liver, by acting as a ceRNA [26,64,114,115]. While the expression of HULC in HCC was previously described to be induced by the transcription factor cAMP response element-binding protein (CREB), there was not much known about the regulation of HULC on the post-transcriptional level [64].…”

Section: Insulin-like Growth Factor 2 Mrna-binding Protein 1 (Igf2bp1)mentioning

confidence: 99%

“…A well-studied example for this is metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), an lncRNA that interacts with serine/arginine (SR) splicing factors, thereby influencing their subnuclear distribution, phosphorylation status, and consequently their activity [20]. Apart from splicing, lncRNAs also regulate mRNA stability and translation by interacting with translation factors and proteins involved in mRNA decay, or by acting as so-called competitive endogenous RNAs (ceRNAs) [23][24][25][26][27]. These ceRNAs sponge up microRNAs (miRNAs) and thus prevent them from binding to and inducing degradation or translational repression of their mRNA targets [25][26][27].According to the NONCODE database (version v5.0), 96,308 lncRNA genes have been identified in the human genome [28].…”

mentioning

confidence: 99%

“…Apart from splicing, lncRNAs also regulate mRNA stability and translation by interacting with translation factors and proteins involved in mRNA decay, or by acting as so-called competitive endogenous RNAs (ceRNAs) [23][24][25][26][27]. These ceRNAs sponge up microRNAs (miRNAs) and thus prevent them from binding to and inducing degradation or translational repression of their mRNA targets [25][26][27].According to the NONCODE database (version v5.0), 96,308 lncRNA genes have been identified in the human genome [28]. Steadily increasing focus is now being put on the functional annotation of these lncRNAs, especially regarding their role in disease [28].…”

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confidence: 99%

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

Jonas

Calin

Pichler

2020

IJMS

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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...

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“…The mice were housed within a dedicated SPF facility. Huh7 stable expressed LINC01234 shRNA1 cells were transplanted subcutaneously in each mouse according to the previous reference (16). The tumor volume was measured weekly according to the reference (17).…”

Section: In Vivo Studymentioning

confidence: 99%

Knockdown of lncRNA LINC01234 suppresses the tumorigenesis of liver cancer via sponging miR-513a-5p

Song

et al. 2020

Preprint

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Background Liver cancer is a frequent malignancy with poor prognosis. It has been reported that many lncRNAs could regulate the progression of liver cancer. To identify potential therapeutic targets for liver cancer, we conducted bioinformatics analysis of lncRNAs in tumor tissues and adjacent normal tissues. Methods The differential expression of lncRNAs between liver cancer tissues and adjacent normal tissues were examined by bioinformatics analysis. Cell proliferation was tested by CCK-8. Cell apoptosis in liver cancer was detected by flow cytometry. Gene and protein expression in liver cancer cells were measured by q-PCR and Western-blot, respectively. Xenograft tumor model was established to verify the function of LNC01234 on liver cancer in vivo. Results LNC01234 was found to be notably upregulated in liver cancer tissues. In addition, knockdown of LNC01234 significantly inhibited the proliferation, invasion and induced the apoptosis of liver cancer cells. Meanwhile, miR-513a-5p was a downstream target of LNC01234 and USP4 was a direct target of miR-513a-5p. Moreover, downregulation of LNC01234 inhibited the tumorigenesis of liver cancer via inactivating TGF-β signaling. Conclusion Downregulation of LNC01234 could inhibit the progression of liver cancer, which may serve as a potential novel target for treatment of liver cancer.

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Long noncoding RNA HULC accelerates the growth of human liver cancer stem cells by upregulating CyclinD1 through miR675-PKM2 pathway via autophagy

Cited by 33 publications

References 55 publications

Identifying Modules of Cooperating Cancer Drivers

Identifying Modules of Cooperating Cancer Drivers

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

Knockdown of lncRNA LINC01234 suppresses the tumorigenesis of liver cancer via sponging miR-513a-5p

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