Multiple myeloma–associated chromosomal translocation activates orphan snoRNA ACA11 to suppress oxidative stress

Chu, Liang; Su, Mack Y.; Maggi, Leonard B.; Lu, Lan; Mullins, Chelsea; Crosby, Seth D.; Huang, Gaofeng; Chng, Wee Joo; Vij, Ravi; Tomasson, Michael H.

doi:10.1172/jci63051

Cited by 94 publications

(140 citation statements)

References 40 publications

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“…Recently, Chu and colleagues revealed oncogenic function of another type of snoRNA, ACA11, which is encoded within introns 18-19 of the WHSC1 gene and demonstrated its function in binding to heterogeneous nuclear ribonucleoproteins rather than the proteins involved in ribosomal biogenesis in multiple myeloma. 22 Furthermore, another study demonstrated that SNORA42 was frequently overexpressed in NSCLC tissues and confirmed its oncogenic function through a series of in vitro and in vivo experiments. In addition, high expression of SNORA42 significantly correlated with poor prognosis in patients with NSCLC, suggesting it to be a potentially relevant diagnostic and therapeutic target in NSCLC.…”

Section: Significance Of This Studymentioning

confidence: 85%

“…18 19 Recently, expression status of SNORD76, SNORD78, ACA11 and SNORA42 were reported to be upregulated in various cancerous tissues. [20][21][22] SNORD76 and SNORD78 are located at 1q25 locus, and are encoded within the intron of a long-coding RNA, growth arrest-specific transcript 5 gene (GAS5). Although increasing body of literature supports the functional role of GAS5 in cancer development, 13 14 23 24 increased expression of GAS5-related snoRNAs, such as SNORD76 and SNORD78, has also been suggested in non-small cell lung cancer (NSCLC) tissues.…”

Section: Significance Of This Studymentioning

confidence: 99%

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Clinical significance of SNORA42 as an oncogene and a prognostic biomarker in colorectal cancer

Okugawa

Toiyama

Toden

et al. 2015

Gut

121

110

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Purpose Despite recent advances in colorectal cancer (CRC) treatment, the prognosis of CRC patients still remains substandard, and metastatic recurrence following curative surgery is the leading cause of poor prognosis. Therefore, it is imperative to identify prognostic markers to predict the clinical outcome of CRC. Recent evidence revealed the new role of small nucleolar RNAs (snoRNAs) in oncogenesis. Herein, we systematically evaluated dysregulation of snoRNAs in CRC, and clarified the biomarker potential and biological significance of snoRNAs in CRC. Experimental Design We analyzed expression levels of four snoRNAs in 274 colorectal tissues from three independent cohorts, and 6 CRC cell lines. The functional characterization for the role of SNORA42 in CRC was investigated through a series of in vitro and in vivo experiments. Results In the screening phase, expression levels of all four snoRNAs were significantly elevated in CRC tissues than in corresponding normal mucosa. In the clinical validation cohort, increased SNORA42 expression was an independent prognostic factor for overall survival and disease free survival, and was an independent risk factor for distant metastasis. SNORA42 expression negatively correlated with overall survival in an additional independent cohort, and identified the patients with high risk for recurrence and poor prognosis in stage II CRC. Furthermore, in vitro and in vivo analysis showed that SNORA42 overexpression resulted in enhanced cell proliferation, migration, invasion, anoikis resistance, and tumorigenicity. Conclusion SNORA42 appears to a novel oncogene and could serve as a promising predictive biomarker for recurrence and prognosis in CRC patients.

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Section: Significance Of This Studymentioning

confidence: 85%

Section: Significance Of This Studymentioning

confidence: 99%

Clinical significance of SNORA42 as an oncogene and a prognostic biomarker in colorectal cancer

Okugawa

Toiyama

Toden

et al. 2015

Gut

121

110

View full text Add to dashboard Cite

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“…These new findings are discussed below. (3), and in direct antiviral effects via a perforin-mediated cytotoxic mechanism (4,5). In this issue of JCI, the Swain group, led by…”

Section: Figurementioning

confidence: 99%

“Snorkeling” for missing players in cancer

Taulli¹,

Pandolfi²

2012

J. Clin. Invest.

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“…Chu et al reported that overexpression of the H/ACA box snoRNA ACA11 in t(4;14)-associated multiple myeloma contributes to myeloma cell proliferation and resistance to chemotherapy. 11 Several groups have reported marked increased expression of snoRNAs contained in the DLK-DIO3 locus in acute promyelocytic leukemia, although their contribution to leukemogenesis is unknown. [12][13][14] The lack of a method to accurately and comprehensively assess snoRNA expression has limited research in this area.…”

Section: Introductionmentioning

confidence: 99%

Expression profiling of snoRNAs in normal hematopoiesis and AML

Warner¹,

Spencer

Trissal³

et al. 2018

Blood Advances

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Key Points• A subset of snoRNAs is expressed in a developmental-and lineage-specific manner during human hematopoiesis.• Neither host gene expression nor alternative splicing accounted for the observed differential expression of snoRNAs in a subset of AML.Small nucleolar RNAs (snoRNAs) are noncoding RNAs that contribute to ribosome biogenesis and RNA splicing by modifying ribosomal RNA and spliceosome RNAs, respectively. We optimized a next-generation sequencing approach and a custom analysis pipeline to identify and quantify expression of snoRNAs in acute myeloid leukemia (AML) and normal hematopoietic cell populations. We show that snoRNAs are expressed in a lineage-and development-specific fashion during hematopoiesis. The most striking examples involve snoRNAs located in 2 imprinted loci, which are highly expressed in hematopoietic progenitors and downregulated during myeloid differentiation. Although most snoRNAs are expressed at similar levels in AML cells compared with CD34 1 , a subset of snoRNAs showed consistent differential expression, with the great majority of these being decreased in the AML samples. Analysis of host gene expression, splicing patterns, and whole-genome sequence data for mutational events did not identify transcriptional patterns or genetic alterations that account for these expression differences. These data provide a comprehensive analysis of the snoRNA transcriptome in normal and leukemic cells and should be helpful in the design of studies to define the contribution of snoRNAs to normal and malignant hematopoiesis.

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Multiple myeloma–associated chromosomal translocation activates orphan snoRNA ACA11 to suppress oxidative stress

Cited by 94 publications

References 40 publications

Clinical significance of SNORA42 as an oncogene and a prognostic biomarker in colorectal cancer

Clinical significance of SNORA42 as an oncogene and a prognostic biomarker in colorectal cancer

“Snorkeling” for missing players in cancer

Expression profiling of snoRNAs in normal hematopoiesis and AML

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