Sequence-specific inhibition of microRNA-130a gene by CRISPR/Cas9 system in breast cancer cell line

MicroRNAs (miRNAs) are short stranded noncoding RNA that play important roles in apoptosis, cell survival, development and cell proliferation. However, gene expression control via small regulatory RNA, particularly miRNA in breast cancer is still less explored. Therefore, this project aims to dev...

Full description

Bibliographic Details
Main Authors: Abdollah, Nur Ainina, Das, Kumitaa Theva, Mohd Yusoff, Narazah, Abdul Razak, Siti Razila
Format: Article
Language:English
Published: IOP Publishing 2017
Subjects:
Online Access:http://eprints.usm.my/37310/
http://eprints.usm.my/37310/1/Abdollah_2017_J._Phys.%253A_Conf._Ser._851_012037.pdf
_version_ 1848878158008287232
author Abdollah, Nur Ainina
Das, Kumitaa Theva
Mohd Yusoff, Narazah
Abdul Razak, Siti Razila
author_facet Abdollah, Nur Ainina
Das, Kumitaa Theva
Mohd Yusoff, Narazah
Abdul Razak, Siti Razila
author_sort Abdollah, Nur Ainina
building USM Institutional Repository
collection Online Access
description MicroRNAs (miRNAs) are short stranded noncoding RNA that play important roles in apoptosis, cell survival, development and cell proliferation. However, gene expression control via small regulatory RNA, particularly miRNA in breast cancer is still less explored. Therefore, this project aims to develop an approach to target microRNA-130a using the Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)/Cas9 system in MCF7, breast cancer cell line. The 20 bp sequences target at stem loop, 3' and 5' end of miR130a were cloned into pSpCas9(BB)-2AGFP (PX458) plasmid, and the positive clones were confirmed by sequencing. A total of 5 μg of PX458-miR130a was transfected to MCF7 using Lipofectamine® 3000 according to manufacturer’s protocol. The transfected cells were maintained in the incubator at 37 ⁰C under humidified 5% CO2. After 48 hours, cells were harvested and total RNA was extracted using miRNeasy Mini Kit (Qiagen). cDNAs were synthesised specific to miR-130a using TaqMan MicroRNA Reverse Transcription Kit (Applied Biosystems). Then, qRT-PCR was carried out using TaqMan Universal Master Mix (Applied Biosystems) to quantify the knockdown level of mature miRNAs in the cells. Result showed that miR-130a-5p was significantly downregulated in MCF7 cell line. However, no significant changes were observed for sequences targeting miR-130a-3p and stem loop. Thus, this study showed that the expression of miR-130a-5p was successfully down-regulated using CRISPR silencing system. This technique may be useful to manipulate the level of miRNA in various cell types to answer clinical questions at the molecular level.
first_indexed 2025-11-15T17:26:53Z
format Article
id usm-37310
institution Universiti Sains Malaysia
institution_category Local University
language English
last_indexed 2025-11-15T17:26:53Z
publishDate 2017
publisher IOP Publishing
recordtype eprints
repository_type Digital Repository
spelling usm-373102017-11-02T03:29:51Z http://eprints.usm.my/37310/ Sequence-specific inhibition of microRNA-130a gene by CRISPR/Cas9 system in breast cancer cell line Abdollah, Nur Ainina Das, Kumitaa Theva Mohd Yusoff, Narazah Abdul Razak, Siti Razila R5-920 Medicine (General) RA440-440.87 Study and teaching. Research MicroRNAs (miRNAs) are short stranded noncoding RNA that play important roles in apoptosis, cell survival, development and cell proliferation. However, gene expression control via small regulatory RNA, particularly miRNA in breast cancer is still less explored. Therefore, this project aims to develop an approach to target microRNA-130a using the Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)/Cas9 system in MCF7, breast cancer cell line. The 20 bp sequences target at stem loop, 3' and 5' end of miR130a were cloned into pSpCas9(BB)-2AGFP (PX458) plasmid, and the positive clones were confirmed by sequencing. A total of 5 μg of PX458-miR130a was transfected to MCF7 using Lipofectamine® 3000 according to manufacturer’s protocol. The transfected cells were maintained in the incubator at 37 ⁰C under humidified 5% CO2. After 48 hours, cells were harvested and total RNA was extracted using miRNeasy Mini Kit (Qiagen). cDNAs were synthesised specific to miR-130a using TaqMan MicroRNA Reverse Transcription Kit (Applied Biosystems). Then, qRT-PCR was carried out using TaqMan Universal Master Mix (Applied Biosystems) to quantify the knockdown level of mature miRNAs in the cells. Result showed that miR-130a-5p was significantly downregulated in MCF7 cell line. However, no significant changes were observed for sequences targeting miR-130a-3p and stem loop. Thus, this study showed that the expression of miR-130a-5p was successfully down-regulated using CRISPR silencing system. This technique may be useful to manipulate the level of miRNA in various cell types to answer clinical questions at the molecular level. IOP Publishing 2017 Article PeerReviewed application/pdf en http://eprints.usm.my/37310/1/Abdollah_2017_J._Phys.%253A_Conf._Ser._851_012037.pdf Abdollah, Nur Ainina and Das, Kumitaa Theva and Mohd Yusoff, Narazah and Abdul Razak, Siti Razila (2017) Sequence-specific inhibition of microRNA-130a gene by CRISPR/Cas9 system in breast cancer cell line. Journal of Physics: Conference Series, 851 (1). pp. 1-6. ISSN 1742-6588 http://iopscience.iop.org/article/10.1088/1742-6596/851/1/012037/pdf
spellingShingle R5-920 Medicine (General)
RA440-440.87 Study and teaching. Research
Abdollah, Nur Ainina
Das, Kumitaa Theva
Mohd Yusoff, Narazah
Abdul Razak, Siti Razila
Sequence-specific inhibition of microRNA-130a gene by CRISPR/Cas9 system in breast cancer cell line
title Sequence-specific inhibition of microRNA-130a gene by CRISPR/Cas9 system in breast cancer cell line
title_full Sequence-specific inhibition of microRNA-130a gene by CRISPR/Cas9 system in breast cancer cell line
title_fullStr Sequence-specific inhibition of microRNA-130a gene by CRISPR/Cas9 system in breast cancer cell line
title_full_unstemmed Sequence-specific inhibition of microRNA-130a gene by CRISPR/Cas9 system in breast cancer cell line
title_short Sequence-specific inhibition of microRNA-130a gene by CRISPR/Cas9 system in breast cancer cell line
title_sort sequence-specific inhibition of microrna-130a gene by crispr/cas9 system in breast cancer cell line
topic R5-920 Medicine (General)
RA440-440.87 Study and teaching. Research
url http://eprints.usm.my/37310/
http://eprints.usm.my/37310/
http://eprints.usm.my/37310/1/Abdollah_2017_J._Phys.%253A_Conf._Ser._851_012037.pdf