Skip to main content

28.09.2016 | Original Paper | Ausgabe 6/2016

Cellular Oncology 6/2016

Identification of genetic variation in the lncRNA HOTAIR associated with HPV16-related cervical cancer pathogenesis

Cellular Oncology > Ausgabe 6/2016
Sweta Sharma Saha, Rahul Roy Chowdhury, Nidhu Ranjan Mondal, Biman Chakravarty, Tanmay Chatterjee, Sudipta Roy, Sharmila Sengupta
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1007/​s13402-016-0298-0) contains supplementary material, which is available to authorized users.


• In-depth analysis of HOTAIR genetic variants and impact on function and expression
• Overrepresentation of rs2366152C among low HOTAIR expressing CaCx cases
• rs2366152C within 3′ LSD1-complex binding-site impairs HOTAIR secondary structure
• rs2366152C facilitates HOTAIR downregulation by gain of miR-22 binding-site
• E7-dependent elevation of miR-22 and rs2366152C results in HOTAIR downregulation



Previously, over-expression of the long noncoding RNA (lncRNA) HOTAIR has been found to be associated with the invasive and metastatic capacities of several epithelial cancers, including cervical cancer (CaCx). Here, we aimed at identifying functionally relevant genetic variants that may be employed to differentiate between clinically distinct CaCx subtypes, i.e., those exhibiting high HOTAIR levels and molecular signatures of metastasis and those lacking such signatures in the presence of low HOTAIR expression levels.


Genomic DNA isolated from various cervical tissue samples (characterized by histopathology and HPV status) was used for HOTAIR amplicon sequencing, followed by validation of the findings by Sanger sequencing. The impact of the genetic variants found on the secondary structure of HOTAIR and the concomitant alterations in miRNA binding sites were determined through in silico analysis, followed by miRNA expression analysis by quantitative real-time PCR and confirmation of miRNA binding using a luciferase reporter assay.


We found that rs2366152C was over-represented [ORage-adjusted = 2.58 (1.23–5.57); p = 0.014] in low HOTAIR expressing HPV positive CaCx cases compared to HPV negative controls. This genetic variant showed the propensity of a secondary structure alteration and gain of a miR-22 binding site in HOTAIR, which was found to be concordant with miR-22 over-expression in low HOTAIR CaCx cases compared to controls. We found that miR-22 expression negatively correlated with HOTAIR and E7 expression in HPV16 positive cases and in an E7 transfected HPV negative CaCx-derived cell line (C33A), but was not altered in high HOTAIR cases compared to controls. Reduced luciferase activity of a HOTAIR rs2366152C expression plasmid in C33A cells through miR-22 co-transfection confirmed the ability of miR-22 to specifically target rs2366152C-harbouring HOTAIR lncRNA in CaCx cells, ultimately leading to its down-regulation.


Our data indicate that rs2366152C not only has the potential to serve as a marker for singling out CaCx cases lacking metastatic molecular signatures, but also to explain the functional inactivation of HOTAIR in these cases, including the mechanism of its down-regulation.

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

e.Med Interdisziplinär

Mit e.Med Interdisziplinär erhalten Sie Zugang zu allen CME-Fortbildungen und Fachzeitschriften auf Zusätzlich können Sie eine Zeitschrift Ihrer Wahl in gedruckter Form beziehen – ohne Aufpreis.

Weitere Produktempfehlungen anzeigen
ESM 1 (DOC 1308 kb)
Über diesen Artikel

Weitere Artikel der Ausgabe 6/2016

Cellular Oncology 6/2016 Zur Ausgabe
  1. Sie können e.Med Innere Medizin 14 Tage kostenlos testen (keine Print-Zeitschrift enthalten). Der Test läuft automatisch und formlos aus. Es kann nur einmal getestet werden.

  2. Das kostenlose Testabonnement läuft nach 14 Tagen automatisch und formlos aus. Dieses Abonnement kann nur einmal getestet werden.

Neu im Fachgebiet Pathologie

22.10.2019 | Schwerpunkt: Seltene Erkrankungen | Ausgabe 6/2019

Die IgG4-assoziierte Erkrankung

Mikroskopische Diagnose und Differenzialdiagnose