Can small nucleolar RNA be a novel molecular target for hepatocellular carcinoma?

Han, Shuwen; Xi, Yang; Qi, Qi; Yin, Jun; Da, Miao

doi:10.1016/j.gene.2020.144384

Cited by 17 publications

(16 citation statements)

References 77 publications

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“…SnoRNAs are a family of conserved RNAs, concentrated in Cajal bodies or nucleoli where they either function in the modification of rRNAs or participate in the processing of rRNAs during ribosomal subunit maturation ( 34 ). Many studies have shown that snoRNA is abnormally regulated in tumors ( 35 – 47 ), and snoRNA or snoRNA host genes can affect the proliferation, apoptosis, invasion and migration of cancer cells ( 37 – 47 ). Okugawa et al and Mei et al found snoRA42 enhance the proliferation, migration, invasion in colorectal cancer (CRC) and Lung cancer ( 41 , 42 ).…”

Section: Discussionmentioning

confidence: 99%

STRAP as a New Therapeutic Target for Poor Prognosis of Pancreatic Ductal Adenocarcinoma Patients Mainly Caused by TP53 Mutation

Chen

et al. 2020

Front. Oncol.

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Pancreatic ductal adenocarcinoma (PDAC) has a high mortality rate and poor prognosis. KRAS , TP53 , CDKN2A , and SMAD4 are driver genes of PDAC and 30–75% patients have mutations in at least two of these four genes. Herein, we analyzed the relationship between these genes and prognosis of 762 patients in the absence of coexisting mutations, using data from three independent public datasets. Interestingly, we found that compared with mutations in other driver genes, TP53 mutation plays a significant role in leading to poor prognosis of PDAC. Additionally, we found that snoRNA-mediated rRNA maturation was responsible for the progression of cancer in PDAC patients with TP53 mutations. Inhibition of STRAP, which regulates the localization of SMN complexes and further affects the assembly of snoRNP, can effectively reduce maturation of rRNA and significantly suppress progression of TP53 -mutant or low p53 expression pancreatic cancer cells in vitro and in vivo . Our study highlighted the actual contribution rate of driver genes to patient prognosis, enriching traditional understanding of the relationship between these genes and PDAC. We also provided a possible mechanism and a new target to combat progression of TP53 -mutant PDAC patients.

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Section: Discussionmentioning

confidence: 99%

STRAP as a New Therapeutic Target for Poor Prognosis of Pancreatic Ductal Adenocarcinoma Patients Mainly Caused by TP53 Mutation

Chen

et al. 2020

Front. Oncol.

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“…Although some snoRNAs have been found in HCC 6 , the genome-wide screening of Upf1-regulated snoRNAs has not been reported, and the specific regulatory mechanisms involving snoRNAs during HCC development are not well understood. Given the close connection between Upf1 and various noncoding RNAs, we speculate that Upf1 may also regulate snoRNAs, as snoRNAs are related to carcinogenesis.…”

Section: Resultsmentioning

confidence: 99%

“…Regarding the function of snoRNAs, they have long been known to modify and make rRNA mature and stable, and this posttranscriptional modification is important for ribosomal biogenesis 5 . Recent studies have shown that snoRNAs can indirectly regulate gene expression by processing to generate small noncoding RNAs, such as miRNAs and piwi-interacting RNAs (piRNAs), and they play an important role in carcinogenesis 6 . snoRNAs can be used as tumor markers and can not only affect the occurrence and development of tumors by affecting the expression of its host genes but also affect the prognosis of tumor patients.…”

Section: Introductionmentioning

confidence: 99%

The C/D box small nucleolar RNA SNORD52 regulated by Upf1 facilitates Hepatocarcinogenesis by stabilizing CDK1

Li¹,

Wu²,

Liu³

et al. 2020

Theranostics

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Rationale: Understanding the roles of small nucleolar RNAs (snoRNAs) in hepatocarcinogenesis will provide new avenues to identify diagnostic and therapeutic targets for hepatocellular carcinoma (HCC). Our previous research confirmed the tumor-suppressive effect of Up-frameshift 1 (Upf1) in HCC. Herein, we examined the expression profiles of snoRNAs regulated by Upf1 in hepatoma cells. Methods: We examined the expression profiles of snoRNAs regulated by Upf1 in hepatoma cells using RNA-sequencing analysis and then investigated the expression and significance of SNORD52 in HCC tissue and different cell lines. The protumorigenic effects of SNORD52 on HCC cells were confirmed both in vitro and in vivo by gain-of-function and loss-of-function assays. RNA pull-down assays and mass spectrometry were used to identify the RNA-binding protein that binds to SNORD52. Results: Many snoRNAs were identified; one of which, the human C/D box small nucleolar RNA SNORD52, was upregulated in HCC tissues and negatively correlated with Upf1 expression, and patients with higher SNORD52 expression had a poor clinical prognosis. SNORD52 promoted HCC tumorigenesis both in vitro and in vivo . Mechanistically, KEGG analysis showed that SNORD52 upregulated a series of cell cycle genes in HCC cells. We further confirmed that SNORD52 upregulated CDK1 by enhancing the stability of CDK1 proteins and that the function of SNORD52 depends on the presence of CDK1. Conclusion: Overall, the present study indicates that SNORD52 could be a potential biomarker for HCC. Targeting the Upf1/SNORD52/CDK1 pathway might have therapeutic potential for HCC.

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“…Of all the host factors involved in this process, ncRNAs, which were once thought to be unimportant, have increasingly been shown to have important regulatory functions in a variety of pathological events, including viral infection (Esteller, 2011;Xu et al, 2019). SnoRNAs are ncRNAs for which a number of have been performed to elucidate the molecular mechanisms associated with their activity function (Mourksi et al, 2020;Shuwen et al, 2020). SnoRNAs typically function as snoRNPs, where specific binding sites on RNAs are provided for core proteins to integrate and work as a stable and functional complex (Massenet et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

“…SnoRNAs are 70–140 nucleotides in length and could form ribonucleoprotein (RNP) complexes with relevant proteins, which are the typical functioning mode of ncRNAs ( Boivin et al, 2018 ). Most snoRNAs play roles in ribosomal RNA modification and processing, the modulation of RNA splicing and translation, and oxidative stress responses ( Matera et al, 2007 ; Shuwen et al, 2020 ). Recently, an increasing number of studies have been carried out to elucidate the molecular mechanism of functional snoRNPs in human diseases, such as cancers or genetic disorders, as well as in many physiological processes ( Stepanov et al, 2015 ; Cavaille, 2017 ; Li et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

SNORD126 Promotes Hepatitis C Virus Infection by Upregulating Claudin-1 via Activation of PI3K-AKT Signaling Pathway

Qian

et al. 2020

Front. Microbiol.

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Hepatitis C virus (HCV) infection involves a variety of viral and host factors, some of which promote the infection process. A small nucleolar RNA, C/D box 126 (SNORD126), was previously shown to be associated with hepatocellular carcinoma (HCC). However, the role of SNORD126 in HCV infection, which is one of the primary reasons for HCC development, has not been elucidated. In the present study, using small nucleolar RNA profiling, we observed that SNORD126 was significantly downregulated during HCV infection in both Huh7 and Huh7.5.1 cells. In addition, overexpression of SNORD126 enhanced HCV entry into host cells, whereas SNORD126 knockdown showed the opposite effect, suggesting that SNORD126 promotes HCV infection, especially through viral entry. Further functional analysis revealed that SNORD126 could enhance the expression level of claudin-1 (CLDN1), a key HCV entry factor, by increasing the levels of phosphorylated AKT. Additionally, the function of SNORD126 in HCV infection was associated with ribonucleoprotein (RNP) complexes. In summary, our findings demonstrate that oncogenic SNORD126 levels are decreased during HCV infection probably due to the host defense reaction, and SNORD126 may be important to promote viral entry by increasing CLDN1 expression through activation of the PI3K-AKT pathway, the mechanism of which is partly associated with SNORD126mediated snoRNA RNP (snoRNP) function. Our work here provides initial evidence that endogenous snoRNA takes part in HCV infection and shows potential as a diagnostic or antiviral agent.

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Can small nucleolar RNA be a novel molecular target for hepatocellular carcinoma?

Cited by 17 publications

References 77 publications

STRAP as a New Therapeutic Target for Poor Prognosis of Pancreatic Ductal Adenocarcinoma Patients Mainly Caused by TP53 Mutation

STRAP as a New Therapeutic Target for Poor Prognosis of Pancreatic Ductal Adenocarcinoma Patients Mainly Caused by TP53 Mutation

The C/D box small nucleolar RNA SNORD52 regulated by Upf1 facilitates Hepatocarcinogenesis by stabilizing CDK1

SNORD126 Promotes Hepatitis C Virus Infection by Upregulating Claudin-1 via Activation of PI3K-AKT Signaling Pathway

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