MALAT1-regulated gene expression profiling in lung cancer cell lines.


Journal

BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800

Informations de publication

Date de publication:
04 Sep 2023
Historique:
received: 14 06 2023
accepted: 28 08 2023
medline: 6 9 2023
pubmed: 5 9 2023
entrez: 4 9 2023
Statut: epublish

Résumé

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and has a poor prognosis. Identifying biomarkers based on molecular mechanisms is critical for early diagnosis, timely treatment, and improved prognosis of lung cancer. MALAT1 has been reported to have overexpressed and tumor-promoting functions in NSCLC. It has been proposed as a potential biomarker for the diagnosis and prognosis of cancer. Therefore, this study was conducted to profile the changes in gene expression according to the regulation of expression of MALAT1 in NSCLC cell lines and to investigate the correlation through bioinformatic analysis of differentially expressed genes (DEGs). MALAT1 expression levels were measured using RT-qPCR. The biological functions of MALAT1 in NSCLC were analyzed by cell counting, colony forming, wound-healing, and Transwell invasion assays. In addition, gene expression profiling in response to the knockdown of MALAT1 was analyzed by transcriptome sequencing, and differentially expressed genes regulated by MALAT1 were performed by GO and KEGG pathway enrichment analyses. Bioinformatic databases were used for gene expression analysis and overall survival analysis. Comparative analysis versus MALAT1 expression in MRC5 cells (a normal lung cell line) and the three NSCLC cell lines showed that MALAT1 expression was significantly higher in the NSCLC cells. MALAT1 knockdown decreased cell survival, proliferation, migration, and invasion in all three NSCLC cell lines. RNA-seq analysis of DEGs in NSCLC cells showed 198 DEGs were upregulated and 266 DEGs downregulated by MALAT1 knockdown in all three NSCLC cell lines. Survival analysis on these common DEGs performed using the OncoLnc database resulted in the selection of five DEGs, phosphoglycerate mutase 1 (PGAM1), phosphoglycerate mutase 4 (PGAM4), nucleolar protein 6 (NOL6), nucleosome assembly protein 1 like 5 (NAP1L5), and sestrin1 (SESN1). The gene expression levels of these selected DEGs were proved to gene expression analysis using the TNMplot database. MALAT1 might function as an oncogene that enhances NSCLC cell survival, proliferation, colony formation, and invasion. RNA-seq and bioinformatic analyses resulted in the selection of five DEGs, PGAM1, PGAM4, NOL6, NAP1L5, and SESN1, which were found to be closely related to patient survival and tumorigenesis. We believe that further investigation of these five DEGs will provide valuable information on the oncogenic role of MALAT1 in NSCLC.

Sections du résumé

BACKGROUND BACKGROUND
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and has a poor prognosis. Identifying biomarkers based on molecular mechanisms is critical for early diagnosis, timely treatment, and improved prognosis of lung cancer. MALAT1 has been reported to have overexpressed and tumor-promoting functions in NSCLC. It has been proposed as a potential biomarker for the diagnosis and prognosis of cancer. Therefore, this study was conducted to profile the changes in gene expression according to the regulation of expression of MALAT1 in NSCLC cell lines and to investigate the correlation through bioinformatic analysis of differentially expressed genes (DEGs).
METHODS METHODS
MALAT1 expression levels were measured using RT-qPCR. The biological functions of MALAT1 in NSCLC were analyzed by cell counting, colony forming, wound-healing, and Transwell invasion assays. In addition, gene expression profiling in response to the knockdown of MALAT1 was analyzed by transcriptome sequencing, and differentially expressed genes regulated by MALAT1 were performed by GO and KEGG pathway enrichment analyses. Bioinformatic databases were used for gene expression analysis and overall survival analysis.
RESULTS RESULTS
Comparative analysis versus MALAT1 expression in MRC5 cells (a normal lung cell line) and the three NSCLC cell lines showed that MALAT1 expression was significantly higher in the NSCLC cells. MALAT1 knockdown decreased cell survival, proliferation, migration, and invasion in all three NSCLC cell lines. RNA-seq analysis of DEGs in NSCLC cells showed 198 DEGs were upregulated and 266 DEGs downregulated by MALAT1 knockdown in all three NSCLC cell lines. Survival analysis on these common DEGs performed using the OncoLnc database resulted in the selection of five DEGs, phosphoglycerate mutase 1 (PGAM1), phosphoglycerate mutase 4 (PGAM4), nucleolar protein 6 (NOL6), nucleosome assembly protein 1 like 5 (NAP1L5), and sestrin1 (SESN1). The gene expression levels of these selected DEGs were proved to gene expression analysis using the TNMplot database.
CONCLUSION CONCLUSIONS
MALAT1 might function as an oncogene that enhances NSCLC cell survival, proliferation, colony formation, and invasion. RNA-seq and bioinformatic analyses resulted in the selection of five DEGs, PGAM1, PGAM4, NOL6, NAP1L5, and SESN1, which were found to be closely related to patient survival and tumorigenesis. We believe that further investigation of these five DEGs will provide valuable information on the oncogenic role of MALAT1 in NSCLC.

Identifiants

pubmed: 37667226
doi: 10.1186/s12885-023-11347-7
pii: 10.1186/s12885-023-11347-7
pmc: PMC10476395
doi:

Substances chimiques

Phosphoglycerate Mutase EC 5.4.2.11
RNA, Long Noncoding 0
MALAT1 long non-coding RNA, human 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

818

Subventions

Organisme : National Research Foundation of Korea
ID : 2022R1A6A3A13072277
Organisme : National Research Foundation of Korea
ID : 2019R1C1C1009423

Informations de copyright

© 2023. BioMed Central Ltd., part of Springer Nature.

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Auteurs

Jungwook Roh (J)

Department of Science Education, Korea National University of Education, Cheongju-si, 28173, Chungbuk, Republic of Korea.

Boseong Kim (B)

Department of Science Education, Korea National University of Education, Cheongju-si, 28173, Chungbuk, Republic of Korea.

Mijung Im (M)

Department of Science Education, Korea National University of Education, Cheongju-si, 28173, Chungbuk, Republic of Korea.

Wonyi Jang (W)

Department of Science Education, Korea National University of Education, Cheongju-si, 28173, Chungbuk, Republic of Korea.

Yeonsoo Chae (Y)

Department of Science Education, Korea National University of Education, Cheongju-si, 28173, Chungbuk, Republic of Korea.

JiHoon Kang (J)

Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory, Emory University School of Medicine, Atlanta, GA, 30322, USA.

BuHyun Youn (B)

Department of Biological Sciences, Pusan National University, Busan, 46241, Republic of Korea.

Wanyeon Kim (W)

Department of Science Education, Korea National University of Education, Cheongju-si, 28173, Chungbuk, Republic of Korea. wykim82@knue.ac.kr.
Department of Biology Education, Korea National University of Education, Cheongju-si, 28173, Chungbuk, Republic of Korea. wykim82@knue.ac.kr.

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