• 17β-estradiol promotes extracellular vesicle release and selective miRNA loading in ERα-positive breast cancer 

      Drula, Rares; Pardini, Barbara; Fu, Xiao; De Los Santos, Mireia Cruz; Jurj, Ancuta; Pang, Lan; El-Daly, Sherien M.; Fabris, Linda; Knutsen, Erik; Dragomir, Mihnea P.; Bayraktar, Recep; Li, Yongfeng; Chen, Meng; Del Vecchio, Filippo; Berland, Léa; Dae, Jessica; Fan, Daniel; Shimizu, Masayoshi; Tran, Anh M.; Barzi, Mercedes; Pioppini, Carlotta; Gutierrez, Angelica M.; Ivan, Cristina; Meas, Salyna; Hall, Carolyn S.; Alahari, Suresh K.; Berindan-Neagoe, Ioana; Fabbri, Muller; Lucci, Anthony; Arun, Banu; Anfossi, Simone; Calin, George A. (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-05-30)
      The causes and consequences of abnormal biogenesis of extracellular vesicles (EVs) are not yet well understood in malignancies, including in breast cancers (BCs). Given the hormonal signaling dependence of estrogen receptor–positive (ER+) BC, we hypothesized that 17β-estradiol (estrogen) might influence EV production and microRNA (miRNA) loading. We report that physiological doses of 17β-estradiol ...
    • ALYREF, a novel factor involved in breast carcinogenesis, acts through transcriptional and post-transcriptional mechanisms selectively regulating the short NEAT1 isoform 

      Klec, Christiane; Knutsen, Erik; Schwarzenbacher, Daniela; Jonas, Katharina; Pasculli, Barbara; Heitzer, Ellen; Rinner, Beate; Krajina, Katarina; Prinz, Felix; Gottschalk, Benjamin; Ulz, Peter; Deutsch, Alexander; Prokesch, Andreas; Jahn, Stephan W.; Lellahi, Seyed Mohammad; Perander, Maria; Barbano, Raffaela; Graier, Wolfgang F.; Parrella, Paola; Calin, George Adrian; Pichler, Martin (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-07-01)
      The RNA-binding protein ALYREF (THOC4) is involved in transcriptional regulation and nuclear mRNA export, though its role and molecular mode of action in breast carcinogenesis are completely unknown. Here, we identifed high ALYREF expression as a factor for poor survival in breast cancer patients. ALYREF signifcantly infuenced cellular growth, apoptosis and mitochondrial energy metabolism in ...
    • Anti–miR-93-5p therapy prolongs sepsis survival by restoring the peripheral immune response 

      Dragomir, Mihnea P.; Fuentes-Mattei, Enrique; Winkle, Melanie; Okubo, Keishi; Bayraktar, Recep; Knutsen, Erik; Qdaisat, Aiham; Chen, Meng; Li, Yongfeng; Shimizu, Masayoshi; Pang, Lan; Liu, Kevin; Liu, Xiuping; Anfossi, Simone; Zhang, Huanyu; Koch, Ines; Tran, Anh M.; Mohapatra, Swati; Ton, Anh; Kaplan, Mecit; Anderson, Matthew W.; Rothfuss, Spencer J.; Silasi, Robert; Keshari, Ravi S.; Ferracin, Manuela; Ivan, Cristina; Rodriguez-Aguayo, Cristian; Lopez-Berestein, Gabriel; Georgescu, Constantin; Banerjee, Pinaki P.; Basar, Rafet; Li, Ziyi; Horst, David; Vasilescu, Catalin; Bertilaccio, Maria Teresa S.; Rezvani, Katayoun; Lupu, Florea; Yeung, Sai-Ching; Calin, George A. (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-06-01)
      Sepsis remains a leading cause of death for humans and currently has no pathogenesis-specific therapy. Hampered progress is partly due to a lack of insight into deep mechanistic processes. In the past decade, deciphering the functions of small noncoding miRNAs in sepsis pathogenesis became a dynamic research topic. To screen for new miRNA targets for sepsis therapeutics, we used samples for miRNA ...
    • Blood Transcriptome Analysis of Septic Patients Reveals a Long Non-Coding Alu-RNA in the Complement C5a Receptor 1 Gene 

      Emblem, Åse; Knutsen, Erik; Jørgensen, Tor Erik; Fure, Hilde; Johansen, Steinar Daae; Brekke, Ole Lars; Mollnes, Tom Eirik; Karlsen, Bård Ove (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-03-29)
      Many severe inflammation conditions are complement-dependent with the complement component C5a-C5aR1 axis as an important driver. At the RNA level, the blood transcriptome undergoes programmed expression of coding and long non-coding RNAs to combat invading microorganisms. Understanding the expression of long non-coding RNAs containing Alu elements in inflammation is important for reconstructing ...
    • Blood Transcriptome Analysis of Septic Patients Reveals a Long Non-Coding Alu-RNA in the Complement C5a Receptor 1 Gene 

      Emblem, Åse; Knutsen, Erik; Jørgensen, Tor Erik; Fure, Hilde; Johansen, Steinar Daae; Brekke, Ole Lars; Mollnes, Tom Eirik; Karlsen, Bård Ove (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-03-29)
      Many severe inflammation conditions are complement-dependent with the complement component C5a-C5aR1 axis as an important driver. At the RNA level, the blood transcriptome undergoes programmed expression of coding and long non-coding RNAs to combat invading microorganisms. Understanding the expression of long non-coding RNAs containing Alu elements in inflammation is important for reconstructing ...
    • Classical and noncanonical functions of miRNAs in cancers 

      Dragomir, Mihnea Paul; Knutsen, Erik; Calin, George A. (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-10-30)
      Alterations in microRNAs (miRNAs) expression are causative in the initiation and progression of human cancers. The molecular events responsible for the widespread differential expression of miRNAs in malignancy are exemplified by their location in cancer-associated genomic regions, epigenetic mechanisms, transcriptional dysregulation, chemical modifications and editing, and alterations in miRNA ...
    • CRISPR/Cas9 to Silence Long Non-Coding RNAs 

      Rosenlund, Ingrid A; Calin, George A.; Dragomir, Mihnea Paul; Knutsen, Erik (Chapter; Bokkapittel, 2021-06-24)
      Knock-out (KO) of long non-coding RNAs (lncRNAs) enables functional characterization of this still poorly described group of transcripts. One of the most efficient and simplest methods to achieve complete KO of a lncRNA is by employing CRISPR/Cas gene editing. As most lncRNAs are not well annotated, their individual functional regions are not defined, and the majority of the transcripts are not ...
    • Current Status of Circulating Tumor Cells, Circulating Tumor DNA, and Exosomes in Breast Cancer Liquid Biopsies 

      Tellez Gabriel, Marta; Knutsen, Erik; Perander, Maria (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-12-11)
      Breast cancer is the most common cancer among women worldwide. Although the five-, ten- and fifteen-year survival rates are good for breast cancer patients diagnosed with early-stage disease, some cancers recur many years after completion of primary therapy. Tumor heterogeneity and clonal evolution may lead to distant metastasis and therapy resistance, which are the main causes of breast cancer-associated ...
    • Differentially Expressed MicroRNAs in Meningiomas Grades I and II Suggest Shared Biomarkers with Malignant Tumors 

      El-Gewely, Mohamed Raafat; Andreassen, Morten; Walquist, Mari; Ursvik, Anita; Knutsen, Erik; Nystad, Mona; Coucheron, Dag H; Myrmel, Kristin Smistad; Hennig, Rune; Johansen, Steinar D (Journal article; Tidsskriftartikkel; Peer reviewed, 2016-03-03)
      Meningiomas represent the most common primary tumors of the central nervous system, but few microRNA (miRNA) profiling studies have been reported so far. Deep sequencing of small RNA libraries generated from two human meningioma biopsies WHO grades I (benign) and II (atypical) were compared to excess dura controls. Nineteen differentially expressed miRNAs were validated by RT-qPCR using tumor RNA ...
    • Direct small RNA signatures in extracellular vesicles from breast cancer cell lines 

      Fiskaa, Tonje; Knutsen, Erik; Nikolaisen, Malene; Jørgensen, Tor Erik; Johansen, Steinar Daae; Perander, Maria; Seternes, Ole Morten (Journal article; Tidsskriftartikkel; Peer reviewed, 2016-08-31)
      Breast cancer is a heterogeneous disease, and different subtypes of breast cancer show distinct cellular morphology, gene expression, metabolism, motility, proliferation, and metastatic potential. Understanding the molecular features responsible for this heterogeneity is important for correct diagnosis and better treatment strategies. Extracellular vesicles (EVs) and their associated molecules ...
    • Disclosing quantitative RT-PCR raw data during manuscript submission: a call for action 

      Untergasser, Andreas; Hellemans, Jan; Pfaffl, Michael W.; Ruijter, Jan M.; van den Hoff, Maurice J. B.; Dragomir, Mihnea P.; Adamoski, Douglas; Dias, Sandra Martha Gomes; Reis, Rui Manuel; Ferracin, Manuela; Dias-Neto, Emmanuel; Marsh, Ian; Kubista, Mikael; Fabbri, Muller; Goel, Ajay; Slabý, Ondřej; Knutsen, Erik; Chen, Baoqing; Negrini, Massimo; Mimori, Koshi; Pichler, Martin; Papatriantafyllou, Maria; Anfossi, Simone; Schmittgen, Thomas D.; Huggett, Jim; Bustin, Stephen; Vandesompele, Jo; Calin, George A. (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-03-14)
      Accuracy and transparency of scientific data are becoming more and more relevant with the increasing concern regarding the evaluation of data reproducibility in many research areas. This concern is also true for quantifying coding and noncoding RNAs, with the remarkable increase in publications reporting RNA profiling and sequencing studies. To address the problem, we propose the following ...
    • Expression and functions of long non-coding RNA NEAT1 and isoforms in breast cancer 

      Knutsen, Erik; Harris, Adrian; Perander, Maria (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-10-20)
      NEAT1 is a highly abundant nuclear architectural long non-coding RNA. There are two overlapping NEAT1 isoforms, NEAT1_1 and NEAT1_2, of which the latter is an essential scaffold for the assembly of a class of nuclear ribonucleoprotein bodies called paraspeckles. Paraspeckle formation is elevated by a wide variety of cellular stressors and in certain developmental processes, either through transcriptional ...
    • The expression of the long NEAT1_2 isoform is associated with human epidermal growth factor receptor 2-positive breast cancers 

      Knutsen, Erik; Lellahi, Seyed Mohammad; Aure, Miriam Ragle; Nord, Silje; Fismen, Silje; Larsen, Kenneth Bowitz; Tellez Gabriel, Marta; Hedberg, Annica; Bjørklund, Sunniva; Bofin, Anna M.; Mælandsmo, Gunhild Mari; Sørlie, Therese; Mortensen, Elin Synnøve; Perander, Maria (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-01-28)
      The long non-coding RNA <i>NEAT1</i> locus is transcribed into two overlapping isoforms, <i>NEAT1_1</i> and <i>NEAT1_2</i>, of which the latter is essential for the assembly of nuclear paraspeckles. <i>NEAT1</i> is abnormally expressed in a wide variety of human cancers. Emerging evidence suggests that the two isoforms have distinct functions in gene expression regulation, and recently it was shown ...
    • FuncPEP: A Database of Functional Peptides Encoded by Non-Coding RNAs 

      Dragomir, Mihnea Paul; Manyam, Ganiraju C; Ott, Leonie Florence; Berland, Léa; Knutsen, Erik; Ivan, Cristina; Lipovich, Leonard; Broom, Bradley M.; Calin, George A (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-09-23)
      Non-coding RNAs (ncRNAs) are essential players in many cellular processes, from normal development to oncogenic transformation. Initially, ncRNAs were defined as transcripts that lacked an open reading frame (ORF). However, multiple lines of evidence suggest that certain ncRNAs encode small peptides of less than 100 amino acids. The sequences encoding these peptides are known as small open reading ...
    • A Holistic Perspective: Exosomes Shuttle between Nerves and Immune Cells in the Tumor Microenvironment 

      Dragomir, Mihnea Paul; Moisoiu, Vlad; Manaila, Roxana; Pardini, Barbara; Knutsen, Erik; Anfossi, Simone; Amit, Moran; Calin, George A. (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-10-31)
      One of the limitations of cancer research has been the restricted focus on tumor cells and the omission of other non-malignant cells that are constitutive elements of this systemic disease. Current research is focused on the bidirectional communication between tumor cells and other components of the tumor microenvironment (TME), such as immune and endothelial cells, and nerves. A major success of ...
    • ICAM1 expression is induced by proinflammatory cytokines and associated with TLS formation in aggressive breast cancer subtypes 

      Figenschau, Stine; Knutsen, Erik; Urbarova, Ilona; Fenton, Christopher Graham; Elston, Bryan; Perander, Maria; Mortensen, Elin Synnøve; Fenton, Kristin Andreassen (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-08-06)
      Intratumoral formation of tertiary lymphoid structures (TLS) within the tumor microenvironment is considered to be a consequence of antigen challenge during anti-tumor responses. Intracellular adhesion molecule 1 (ICAM1) has been implicated in a variety of immune and inflammatory responses, in addition to associate with triple negative breast cancer (TNBC). In this study, we detected TLS in the ...
    • Identification of a core EMT signature that separates basal-like breast cancers into partial- and post-EMT subtypes 

      Knutsen, Erik; Sajib, Saikat Das; Fiskaa, Tonje; Lorens, James Bradley; Gudjonsson, Thorarinn; Mælandsmo, Gunhild Mari; Johansen, Steinar Daae; Seternes, Ole Morten; Perander, Maria (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-12-04)
      Epithelial-mesenchymal transition (EMT) is a cellular plasticity program critical for embryonic development and tissue regeneration, and aberrant EMT is associated with disease including cancer. The high degree of plasticity in the mammary epithelium is reflected in extensive heterogeneity among breast cancers. Here, we have analyzed RNA-sequencing data from three different mammary epithelial cell ...
    • The long noncoding RNA CCAT2 induces chromosomal instability through BOP1-AURKB signaling 

      Chen, Baoqing; Dragomir, Mihnea Paul; Fabris, Linda; Bayraktar, Recep; Knutsen, Erik; Liu, Xu; Tang, Changyan; Li, Yongfeng; Shimura, Tadanobu; Ivkovic, Tina Catela; Cruz De los Santos, Mireia; Anfossi, Simone; Shimizu, Masayoshi; Shah, Maitri Y.; Ling, Hui; Shen, Peng; Multani, Asha S.; Pardini, Barbara; Burks, Jared K.; Katayama, Hiroyuki; Reineke, Lucas C.; Huo, Longfei; Syed, Muddassir; Song, Shumei; Ferracin, Manuela; Oki, Eiji; Fromm, Bastian; Ivan, Cristina; Bhuvaneshwar, Krithika; Gusev, Yuriy; Mimori, Koshi; Menter, David; Sen, Subrata; Matsuyama, Takatoshi; Uetake, Hiroyuki; Vasilescu, Catalin; Kopetz, Scott; Parker-Thornburg, Jan; Taguchi, Ayumu; Hanash, Samir M.; Girnita, Leonard; Slaby, Ondrej; Goel, Ajay; Varani, Gabriele; Gagea, Mihai; Li, Chunlai; Ajani, Jaffer A.; Calin, George A. (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-08-15)
      Background & Aims - Chromosomal instability (CIN) is a carcinogenesis event that promotes metastasis and resistance to therapy by unclear mechanisms. Expression of the colon cancer–associated transcript 2 gene (CCAT2), which encodes a long noncoding RNA (lncRNA), associates with CIN, but little is known about how CCAT2 lncRNA regulates this cancer enabling characteristic.<p> <p>Methods - We ...
    • The long noncoding RNA NEAT1 and nuclear paraspeckles are up-regulated by the transcription factor HSF1 in the heat shock response 

      Lellahi, Seyed Mohammad; Rosenlund, Ingrid Arctander; Hedberg, Annica; Kiær, Liv Torill; Mikkola, Ingvild; Knutsen, Erik; Perander, Maria (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-10-10)
      The long noncoding RNA (lncRNA) <i>NEAT1</i> (nuclear enriched abundant transcript 1) is the architectural component of nuclear paraspeckles, and it has recently gained considerable attention as it is abnormally expressed in pathological conditions such as cancer and neurodegenerative diseases. <i>NEAT1</i> and paraspeckle formation are increased in cells upon exposure to a variety of environmental ...
    • Metabolic re-wiring of isogenic breast epithelial cell lines following epithelial to mesenchymal transition 

      Haldorsson, Skarphedinn; Rohatgi, Neha; Magnusdottir, Manuela; Choudhary, Kumari; Gudjónsson, Thorarinn; Knutsen, Erik; Barkovskaya, Anna; Hilmarsdòttir, Bylgja; Perander, Maria; Mælandsmo, Gunhild; Gudmundsson, Steinn; Rolfsson, Ottar (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-03-18)
      Epithelial to mesenchymal transition (EMT) has implications in tumor progression and metastasis. Metabolic alterations have been described in cancer development but studies focused on the metabolic re-wiring that takes place during EMT are still limited. We performed metabolomics profiling of a breast epithelial cell line and its EMT derived mesenchymal phenotype to create genome-scale metabolic ...