Targeting miR-9 in gastric cancer cells using locked nucleic acid oligonucleotides

Joana Filipa Lima*, Joana Carvalho, Inês Pinto-Ribeiro, Carina Almeida, Jesper Wengel, Laura Cerqueira, Céu Figueiredo, Carla Oliveira, Nuno Filipe Azevedo

*Corresponding author for this work

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Abstract

Background: Gastric cancer is the third leading cause of cancer-related mortality worldwide. Recently, it has been demonstrated that gastric cancer cells display a specific miRNA expression profile, with increasing evidence of the role of miRNA-9 in this disease. miRNA-9 upregulation has been shown to influence the expression of E-cadherin-encoding gene, triggering cell motility and invasiveness. Results: In this study, we designed LNA anti-miRNA oligonucleotides with a complementary sequence to miRNA-9 and tested their properties to both detect and silence the target miRNA. We could identify and visualize the in vitro uptake of low-dosing LNA-based anti-miRNA oligonucleotides without any carrier or transfection agent, as early as 2h after the addition of the oligonucleotide sequence to the culture medium. Furthermore, we were able to assess the silencing potential of miRNA-9, using different LNA anti-miRNA oligonucleotide designs, and to observe its subsequent effect on E-cadherin expression. Conclusions: The administration of anti-miRNA sequences even at low-doses, rapidly repressed the target miRNA, and influenced the expression of E-cadherin by significantly increasing its levels.

Original languageEnglish
Article number6
JournalBMC Molecular Biology
Volume19
Number of pages13
ISSN1471-2199
DOIs
Publication statusPublished - 7. Jun 2018

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MicroRNAs
Cell Movement
Culture Media
Up-Regulation

Keywords

  • E-cadherin
  • FISH
  • LNA-AMOs
  • Locked nucleic acid
  • MicroRNA
  • MiR-9
  • Down-Regulation
  • Humans
  • Gene Expression Regulation, Neoplastic/drug effects
  • Cell Survival/drug effects
  • Oligonucleotides/pharmacology
  • Stomach Neoplasms/drug therapy
  • Cadherins/genetics
  • Cell Line, Tumor
  • Cell Proliferation/drug effects
  • MicroRNAs/antagonists & inhibitors
  • Antigens, CD

Cite this

Lima, J. F., Carvalho, J., Pinto-Ribeiro, I., Almeida, C., Wengel, J., Cerqueira, L., ... Azevedo, N. F. (2018). Targeting miR-9 in gastric cancer cells using locked nucleic acid oligonucleotides. BMC Molecular Biology, 19, [6]. https://doi.org/10.1186/s12867-018-0107-6
Lima, Joana Filipa ; Carvalho, Joana ; Pinto-Ribeiro, Inês ; Almeida, Carina ; Wengel, Jesper ; Cerqueira, Laura ; Figueiredo, Céu ; Oliveira, Carla ; Azevedo, Nuno Filipe. / Targeting miR-9 in gastric cancer cells using locked nucleic acid oligonucleotides. In: BMC Molecular Biology. 2018 ; Vol. 19.
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author = "Lima, {Joana Filipa} and Joana Carvalho and In{\^e}s Pinto-Ribeiro and Carina Almeida and Jesper Wengel and Laura Cerqueira and C{\'e}u Figueiredo and Carla Oliveira and Azevedo, {Nuno Filipe}",
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Lima, JF, Carvalho, J, Pinto-Ribeiro, I, Almeida, C, Wengel, J, Cerqueira, L, Figueiredo, C, Oliveira, C & Azevedo, NF 2018, 'Targeting miR-9 in gastric cancer cells using locked nucleic acid oligonucleotides', BMC Molecular Biology, vol. 19, 6. https://doi.org/10.1186/s12867-018-0107-6

Targeting miR-9 in gastric cancer cells using locked nucleic acid oligonucleotides. / Lima, Joana Filipa; Carvalho, Joana; Pinto-Ribeiro, Inês; Almeida, Carina; Wengel, Jesper; Cerqueira, Laura; Figueiredo, Céu; Oliveira, Carla; Azevedo, Nuno Filipe.

In: BMC Molecular Biology, Vol. 19, 6, 07.06.2018.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Targeting miR-9 in gastric cancer cells using locked nucleic acid oligonucleotides

AU - Lima, Joana Filipa

AU - Carvalho, Joana

AU - Pinto-Ribeiro, Inês

AU - Almeida, Carina

AU - Wengel, Jesper

AU - Cerqueira, Laura

AU - Figueiredo, Céu

AU - Oliveira, Carla

AU - Azevedo, Nuno Filipe

PY - 2018/6/7

Y1 - 2018/6/7

N2 - Background: Gastric cancer is the third leading cause of cancer-related mortality worldwide. Recently, it has been demonstrated that gastric cancer cells display a specific miRNA expression profile, with increasing evidence of the role of miRNA-9 in this disease. miRNA-9 upregulation has been shown to influence the expression of E-cadherin-encoding gene, triggering cell motility and invasiveness. Results: In this study, we designed LNA anti-miRNA oligonucleotides with a complementary sequence to miRNA-9 and tested their properties to both detect and silence the target miRNA. We could identify and visualize the in vitro uptake of low-dosing LNA-based anti-miRNA oligonucleotides without any carrier or transfection agent, as early as 2h after the addition of the oligonucleotide sequence to the culture medium. Furthermore, we were able to assess the silencing potential of miRNA-9, using different LNA anti-miRNA oligonucleotide designs, and to observe its subsequent effect on E-cadherin expression. Conclusions: The administration of anti-miRNA sequences even at low-doses, rapidly repressed the target miRNA, and influenced the expression of E-cadherin by significantly increasing its levels.

AB - Background: Gastric cancer is the third leading cause of cancer-related mortality worldwide. Recently, it has been demonstrated that gastric cancer cells display a specific miRNA expression profile, with increasing evidence of the role of miRNA-9 in this disease. miRNA-9 upregulation has been shown to influence the expression of E-cadherin-encoding gene, triggering cell motility and invasiveness. Results: In this study, we designed LNA anti-miRNA oligonucleotides with a complementary sequence to miRNA-9 and tested their properties to both detect and silence the target miRNA. We could identify and visualize the in vitro uptake of low-dosing LNA-based anti-miRNA oligonucleotides without any carrier or transfection agent, as early as 2h after the addition of the oligonucleotide sequence to the culture medium. Furthermore, we were able to assess the silencing potential of miRNA-9, using different LNA anti-miRNA oligonucleotide designs, and to observe its subsequent effect on E-cadherin expression. Conclusions: The administration of anti-miRNA sequences even at low-doses, rapidly repressed the target miRNA, and influenced the expression of E-cadherin by significantly increasing its levels.

KW - E-cadherin

KW - FISH

KW - LNA-AMOs

KW - Locked nucleic acid

KW - MicroRNA

KW - MiR-9

KW - Down-Regulation

KW - Humans

KW - Gene Expression Regulation, Neoplastic/drug effects

KW - Cell Survival/drug effects

KW - Oligonucleotides/pharmacology

KW - Stomach Neoplasms/drug therapy

KW - Cadherins/genetics

KW - Cell Line, Tumor

KW - Cell Proliferation/drug effects

KW - MicroRNAs/antagonists & inhibitors

KW - Antigens, CD

U2 - 10.1186/s12867-018-0107-6

DO - 10.1186/s12867-018-0107-6

M3 - Journal article

C2 - 29879907

AN - SCOPUS:85048131114

VL - 19

JO - B M C Molecular Biology

JF - B M C Molecular Biology

SN - 1471-2199

M1 - 6

ER -