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      LINC00511 exacerbated T-cell acute lymphoblastic leukemia via miR-195-5p/LRRK1 axis

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          Abstract

          T-cell acute lymphoblastic leukemia (T-ALL) is a malignant disease arising from the abnormal proliferation of T lymphocyte in marrow. Long non-coding RNAs (lncRNAs) are one kind of non-coding RNAs (ncRNAs), which were reported to modulate the initiation or progression of diverse cancers. However, the role of LINC00511 in T-ALL was unknown. To figure out the function and mechanism of LINC00511 in T-ALL, a series of experiments were carried out. Based on the experimental results, we discovered that LINC00511 boosted cell proliferation and invasion, but hindered cell apoptosis in T-ALL cells. Besides, based on bio-informatics tool, miR-195-5p was selected for further exploration. Then, miR-195-5p was validated to bind with LINC00511. Hereafter, LRRK1 was testified to serve as a target gene of miR-195-5p. At last, rescue assays suggested that LRRK1 overexpression restored sh-LINC00511#1-mediated effects on cell proliferation and apoptosis. All in all, LINC00511 exacerbated T-ALL progression via miR-195-5p/LRRK1 axis, implying a potential therapeutic clue for the patients with T-ALL.

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          Long Noncoding RNA and Cancer: A New Paradigm.

          Milad Soleimani, Subhrangsu Mandal, Arunoday Bhan (2017)
          In addition to mutations or aberrant expression in the protein-coding genes, mutations and misregulation of noncoding RNAs, in particular long noncoding RNAs (lncRNA), appear to play major roles in cancer. Genome-wide association studies of tumor samples have identified a large number of lncRNAs associated with various types of cancer. Alterations in lncRNA expression and their mutations promote tumorigenesis and metastasis. LncRNAs may exhibit tumor-suppressive and -promoting (oncogenic) functions. Because of their genome-wide expression patterns in a variety of tissues and their tissue-specific expression characteristics, lncRNAs hold strong promise as novel biomarkers and therapeutic targets for cancer. In this article, we have reviewed the emerging functions and association of lncRNAs in different types of cancer and discussed their potential implications in cancer diagnosis and therapy. Cancer Res; 77(15); 3965-81. ©2017 AACR.
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            History, Discovery, and Classification of lncRNAs.

            Marina Pinskaya, Antonin Morillon, Julien Jarroux (2017)
            The RNA World Hypothesis suggests that prebiotic life revolved around RNA instead of DNA and proteins. Although modern cells have changed significantly in 4 billion years, RNA has maintained its central role in cell biology. Since the discovery of DNA at the end of the nineteenth century, RNA has been extensively studied. Many discoveries such as housekeeping RNAs (rRNA, tRNA, etc.) supported the messenger RNA model that is the pillar of the central dogma of molecular biology, which was first devised in the late 1950s. Thirty years later, the first regulatory non-coding RNAs (ncRNAs) were initially identified in bacteria and then in most eukaryotic organisms. A few long ncRNAs (lncRNAs) such as H19 and Xist were characterized in the pre-genomic era but remained exceptions until the early 2000s. Indeed, when the sequence of the human genome was published in 2001, studies showed that only about 1.2% encodes proteins, the rest being deemed "non-coding." It was later shown that the genome is pervasively transcribed into many ncRNAs, but their functionality remained controversial. Since then, regulatory lncRNAs have been characterized in many species and were shown to be involved in processes such as development and pathologies, revealing a new layer of regulation in eukaryotic cells. This newly found focus on lncRNAs, together with the advent of high-throughput sequencing, was accompanied by the rapid discovery of many novel transcripts which were further characterized and classified according to specific transcript traits.In this review, we will discuss the many discoveries that led to the study of lncRNAs, from Friedrich Miescher's "nuclein" in 1869 to the elucidation of the human genome and transcriptome in the early 2000s. We will then focus on the biological relevance during lncRNA evolution and describe their basic features as genes and transcripts. Finally, we will present a non-exhaustive catalogue of lncRNA classes, thus illustrating the vast complexity of eukaryotic transcriptomes.
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              Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study.

              Max Topp, Nicola Gökbuget, Anthony S. Stein … (2015)
              Adults with relapsed or refractory B-precursor acute lymphoblastic leukaemia have an unfavourable prognosis. Blinatumomab is a bispecific T-cell engager antibody construct targeting CD19, an antigen consistently expressed on B-lineage acute lymphoblastic leukaemia cells. We aimed to confirm the activity and safety profile of blinatumomab for acute lymphoblastic leukaemia. In a multicentre, single-arm, open-label phase 2 study, we enrolled adult patients with Philadelphia-chromosome-negative, primary refractory or relapsed (first relapse within 12 months of first remission, relapse within 12 months after allogeneic haemopoietic stem-cell transplantation [HSCT], or no response to or relapse after first salvage therapy or beyond) leukaemia. Patients received blinatumomab (9 μg/day for the first 7 days and 28 μg/day thereafter) by continuous intravenous infusion over 4 weeks every 6 weeks (up to five cycles), per protocol. The primary endpoint was complete remission (CR) or CR with partial haematological recovery of peripheral blood counts (CRh) within the first two cycles. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, number NCT01466179. Between Jan 13, 2012, and Oct 10, 2013, 189 patients were enrolled and treated with blinatumomab. After two cycles, 81 (43%, 95% CI 36-50) patients had achieved a CR or CRh: 63 (33%) patients had a CR and 18 (10%) patients had a CRh. 32 (40%) of patients who achieved CR/CRh underwent subsequent allogeneic HSCT. The most frequent grade 3 or worse adverse events were febrile neutropenia (48 patients, 25%), neutropenia (30 patients, 16%), and anaemia (27 patients, 14%). Three (2%) patients had grade 3 cytokine release syndrome. Neurologic events of worst grade 3 or 4 occurred in 20 (11%) and four (2%) patients, respectively. Three deaths (due to sepsis, Escherichia coli sepsis, and Candida infection) were thought to be treatment-related by the investigators. Single-agent blinatumomab showed antileukaemia activity in adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia characterised by negative prognostic factors. Further assessment of blinatumomab treatment earlier in the course of the disease and in combination with other treatment approaches is warranted. Amgen. Copyright © 2015 Elsevier Ltd. All rights reserved.
              Article 0 comments Cited 231 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Xinxin Xu:
                ORCID: http://orcid.org/0000-0003-2824-208X
                Journal
                Journal ID (nlm-ta): Biosci Rep
                Journal ID (iso-abbrev): Biosci Rep
                Journal ID (publisher-id): bsr
                Title: Bioscience Reports
                Publisher: Portland Press Ltd.
                ISSN (Print): 0144-8463
                ISSN (Electronic): 1573-4935
                Publication date Collection: 29 May 2020
                Publication date (Electronic): 07 May 2020
                Volume: 40
                Issue: 5
                Electronic Location Identifier: BSR20193631
                Affiliations
                [1 ]Department of Hematology, Jining No.1 People’s Hospital, No. 6 Health Road, Rencheng District, Jining 272100, Shandong, China
                [2 ]Department of Hematology, Dongchangfu People’s Hospital of Liaocheng, 281 Dongguan Street, Dongchangfu District, Liaocheng 252000, Shandong, China
                [3 ]Department of Emergency, Zi Bo Central Hospital, 54 Communist Youth League West Road, Zhangdian District, Zibo 255000, Shandong, China
                [4 ]Department of Hematology, Zi Bo Central Hospital, 54 Communist Youth League West Road, Zhangdian District, Zibo, 255000 Shandong, China
                Author notes
                Correspondence: Xinxin Xu ( 285368240@ 123456qq.com )
                Author information
                http://orcid.org/0000-0003-2824-208X
                Article
                Publisher ID: BSR20193631
                DOI: 10.1042/BSR20193631
                PMC ID: 7953487
                PubMed ID: 32242897
                SO-VID: cba4787b-db24-49f5-8eb0-ccd0f7e41b59
                Copyright © © 2020 The Author(s).
                License:

                This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY).

                History
                Date received : 14 October 2019
                Date revision received : 10 February 2020
                Date accepted : 17 February 2020
                Date: 03 April 2020
                Page count
                Pages: 11
                Categories
                Subject: Biotechnology
                Subject: Cardiovascular System & Vascular Biology
                Subject: Gene Expression & Regulation
                Subject: Genomics
                Subject: Pharmacology & Toxicology
                Subject: Research Articles

                ScienceOpen disciplines: Life sciences
                Keywords: linc00511,lrrk1,mir-195-5p,t-cell acute lymphoblastic leukemia
                Data availability:
                ScienceOpen disciplines: Life sciences
                Keywords: linc00511, lrrk1, mir-195-5p, t-cell acute lymphoblastic leukemia

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