Overexpression of LncRNA MNX1-AS1/PPFIA4 Activates AKT/HIF-1 <i>α</i> Signal Pathway to Promote Stemness of Colorectal Adenocarcinoma Cells

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Abstract

Purpose

The purpose of this study was to explore the role of the lncRNA MNX1-AS1 and its related downstream signaling pathways in colorectal adenocarcinoma (COAD).

Methods

COAD tissues and cells were prepared and treated with sh-MNX1-AS1, pcDNA-MNX1-AS1, sh-PPFIA4, LY29004, and their controls. CCK8 and colony formation assays were undertaken for evaluating cell proliferation. Tumor cell migratory ability was detected by transwell assay. Apoptosis detection was processed by YO-PRO-1/PI Staining. The regulated relationship between lncRNA MNX1-AS1 and PPFIA4 was confirmed by RIP-ChIP assay. Q-PCR was applied to detect genes related to tumor cell stemness, proliferation, migration, and apoptosis in each group. Finally, a xenograft tumor model was constructed to verify the result in vivo.

Results

COAD patients with high expression of the lncRNA MNX1-AS1 have poor prognosis. LncRNA MNX1-AS1 promotes the stemness of COAD cells. PPFIA4 mediates lncRNA MNX1-AS1 expression and affects COAD cell stemness. LncRNA MNX1-AS1 accelerates proliferation and migration, while it suppresses apoptosis. LncRNA MNX1-AS1/PPFIA4 accelerates tumor growth in COAD model. LncRNA MNX1-AS1/PPFIA4 activates the downstream AKT/HIF-1 α signaling pathway to promote COAD development. LY29004 significantly inhibits the tumorigenic ability of lncRNA MNX1-AS1 and PPFIA4.

Conclusion

LncRNA MNX1-AS1/PPFIA4 activates AKT/HIF-1 α signal pathway to promote the stemness of COAD cells, which could be a new target for COAD treatment.

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Most cited references 46

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GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses

Zefang Tang, Chenwei Li, Boxi Kang … (2017)

Abstract Tremendous amount of RNA sequencing data have been produced by large consortium projects such as TCGA and GTEx, creating new opportunities for data mining and deeper understanding of gene functions. While certain existing web servers are valuable and widely used, many expression analysis functions needed by experimental biologists are still not adequately addressed by these tools. We introduce GEPIA (Gene Expression Profiling Interactive Analysis), a web-based tool to deliver fast and customizable functionalities based on TCGA and GTEx data. GEPIA provides key interactive and customizable functions including differential expression analysis, profiling plotting, correlation analysis, patient survival analysis, similar gene detection and dimensionality reduction analysis. The comprehensive expression analyses with simple clicking through GEPIA greatly facilitate data mining in wide research areas, scientific discussion and the therapeutic discovery process. GEPIA fills in the gap between cancer genomics big data and the delivery of integrated information to end users, thus helping unleash the value of the current data resources. GEPIA is available at http://gepia.cancer-pku.cn/.

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starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein–RNA interaction networks from large-scale CLIP-Seq data

Jun-Hao Li, Shun Liu, Hui Zhou … (2013)

Although microRNAs (miRNAs), other non-coding RNAs (ncRNAs) (e.g. lncRNAs, pseudogenes and circRNAs) and competing endogenous RNAs (ceRNAs) have been implicated in cell-fate determination and in various human diseases, surprisingly little is known about the regulatory interaction networks among the multiple classes of RNAs. In this study, we developed starBase v2.0 (http://starbase.sysu.edu.cn/) to systematically identify the RNA–RNA and protein–RNA interaction networks from 108 CLIP-Seq (PAR-CLIP, HITS-CLIP, iCLIP, CLASH) data sets generated by 37 independent studies. By analyzing millions of RNA-binding protein binding sites, we identified ∼9000 miRNA-circRNA, 16 000 miRNA-pseudogene and 285 000 protein–RNA regulatory relationships. Moreover, starBase v2.0 has been updated to provide the most comprehensive CLIP-Seq experimentally supported miRNA-mRNA and miRNA-lncRNA interaction networks to date. We identified ∼10 000 ceRNA pairs from CLIP-supported miRNA target sites. By combining 13 functional genomic annotations, we developed miRFunction and ceRNAFunction web servers to predict the function of miRNAs and other ncRNAs from the miRNA-mediated regulatory networks. Finally, we developed interactive web implementations to provide visualization, analysis and downloading of the aforementioned large-scale data sets. This study will greatly expand our understanding of ncRNA functions and their coordinated regulatory networks.

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UALCAN: An update to the integrated cancer data analysis platform

Darshan Chandrashekar, Santhosh Karthikeyan, Praveen Korla … (2022)

Cancer genomic, transcriptomic, and proteomic profiling has generated extensive data that necessitate the development of tools for its analysis and dissemination. We developed UALCAN to provide a portal for easy exploring, analyzing, and visualizing these data, allowing users to integrate the data to better understand the gene, proteins, and pathways perturbed in cancer and make discoveries. UALCAN web portal enables analyzing and delivering cancer transcriptome, proteomics, and patient survival data to the cancer research community. With data obtained from The Cancer Genome Atlas (TCGA) project, UALCAN has enabled users to evaluate protein-coding gene expression and its impact on patient survival across 33 types of cancers. The web portal has been used extensively since its release and received immense popularity, underlined by its usage from cancer researchers in more than 100 countries. The present manuscript highlights the task we have undertaken and updates that we have made to UALCAN since its release in 2017. Extensive user feedback motivated us to expand the resource by including data on a) microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and promoter DNA methylation from TCGA and b) mass spectrometry-based proteomics from the Clinical Proteomic Tumor Analysis Consortium (CPTAC). UALCAN provides easy access to pre-computed, tumor subgroup-based gene/protein expression, promoter DNA methylation status, and Kaplan-Meier survival analyses. It also provides new visualization features to comprehend and integrate observations and aids in generating hypotheses for testing. UALCAN is accessible at http://ualcan.path.uab.edu

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Author and article information

Contributors

Wei Zhao:

ORCID: https://orcid.org/0000-0003-2421-7311

Hao Hu:

ORCID: https://orcid.org/0000-0001-9271-2897

Journal

Journal ID (nlm-ta): J Oncol

Journal ID (iso-abbrev): J Oncol

Journal ID (publisher-id): jo

Title: Journal of Oncology

Publisher: Hindawi

ISSN (Print): 1687-8450

ISSN (Electronic): 1687-8469

Publication date Collection: 2022

Publication date (Electronic): 3 October 2022

Volume: 2022

Electronic Location Identifier: 8303409

Affiliations

¹Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province 215006, China

²Department of General Surgery, Jiangyin People's Hospital Affiliated to Nantong University, No. 163 Shoushan Rd, Jiangyin, Jiangsu Province 214400, China

³Department of Clinical Biochemistry, School of Laboratory Medicine, Chengdu Medical College, No. 783, Xindu Rd., Chengdu, Sichuan 610500, China

Author notes

Academic Editor: Dong-Hua Yang

Author information

Qi Sun https://orcid.org/0000-0003-3013-5451

Zhenguo Zhao https://orcid.org/0000-0003-1230-3116

Wenlong Xu https://orcid.org/0000-0002-5022-1878

JunJia Zhu https://orcid.org/0000-0002-5809-9897

Wei Zhao https://orcid.org/0000-0003-2421-7311

Hao Hu https://orcid.org/0000-0001-9271-2897

Article

DOI: 10.1155/2022/8303409

PMC ID: 9550508

PubMed ID: 36226248

SO-VID: 59577f01-a72d-4e64-8f47-7b623ecc2799

License:

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 24 August 2022

Date accepted : 16 September 2022

Funding

Funded by: Chengdu Medical College

Award ID: CMC-XK-2103

Funded by: Scientific Research Project of Jiangyin Health Commission

Award ID: S202002

Funded by: Wuxi Precision Medicine Project

Award ID: J202009

Funded by: Wuxi “Taihu Lake Talent Plan” Medical and Health High Level Talent Project

Award ID: NO2020103

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Overexpression of LncRNA MNX1-AS1/PPFIA4 Activates AKT/HIF-1 α Signal Pathway to Promote Stemness of Colorectal Adenocarcinoma Cells

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Abstract

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Conclusion

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Karger: Oncology

Most cited references 46

GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses

starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein–RNA interaction networks from large-scale CLIP-Seq data

UALCAN: An update to the integrated cancer data analysis platform

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