Long non-coding RNA MALAT1 as a key target in pathogenesis of glioblastoma. Janus faces or Achilles’ heal?

• Published in: Gene 2020-05, Vol.739, p.144518-144518, Article 144518
• Main Authors: Baspinar, Yucel, Elmaci, Ilhan, Ozpinar, Aysel, Altinoz, Meric A.
• Format: Article
• Language: English
• Subjects: Brain Neoplasms - diagnosis; Brain Neoplasms - genetics; Brain Neoplasms - therapy; Glioblastoma; Glioblastoma - diagnosis; Glioblastoma - genetics; Glioblastoma - therapy; Humans; lncRNA; MALAT1; microRNA; MicroRNAs - genetics; MicroRNAs - metabolism; Nestin - genetics; Nestin - metabolism; Prognosis; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; SOXB1 Transcription Factors - genetics; SOXB1 Transcription Factors - metabolism; Wnt Signaling Pathway - genetics
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2020.144518

•LncRNAs (Long-noncoding RNAs) involve in versatile biological pathways.•LncRNA MALAT1 propagates growth of glioblastoma (GBM).•Opposite findings also exist regarding MALAT-1 functioning in GBM.•MALAT1 involves in stemness of GBM cells by regulating SOX2, nestin and WNT pathway.•MALAT1 deserves to be studied further as an important therapeutic target in GBM. Glioblastomas (GBMs) are primary brain tumors with extremely bad prognosis and therefore; discovery of novel regulators of their pathology is of immense importance. LncRNAs (long noncoding RNAs) regulate nuclear structure, embryonic pluripotency, cell differentiation, development and carcinogenesis. Many lncRNAs have weak evolutionary conservation; however, a nuclear lncRNA, MALAT1 (metastasis-associated lung adenocarcinoma transcript 1), is exceptionally conserved and is among the most abundant lncRNAs in benign tissues. The majority of cell culture studies and clinico-epidemiological studies demonstrated that MALAT1 acts a tumor promoter in GBMs and inhibition of MALAT1 suppressed tumor growth in various preclinical models of GBM. MALAT1 involves in stemness of GBM cells by regulating SOX2, nestin and members of WNT pathway. MALAT1 induces protective autophagy and suppresses apoptosis in GBM cells via sponging miRNA-101 and increases temozolomide chemoresistance via enhancing epithelial-mesenchymal transition, suppressing miR-203 and promoting thymidilate synthase. Moreover, knockdown of MALAT1 expression enhances blood-brain tumor barrier permeability via miR-140, which may provide a double benefit of MALAT1 suppression by increasing the delivery of chemotherapy agents into the GBM tissues. On the other hand, there also exist some cell culture and animal studies showing that MALAT1 acts as a tumor suppressor in GBMs by suppression of ERK/MAPK and MMP2 signaling and by repression of miR-155 with subsequent increase of FBXW7. Whether protective or detrimental, MALAT1 seems to be an important component of GBM pathogenesis and hence; novels studies are needed in versatile models, including many different primary GBM cultures, orthotopic and xenogreft in vivo models and transgenic mice.