Construction of a paclitaxel-related competitive endogenous RNA network and identification of a potential regulatory axis in pancreatic cancer

Author(s): Si Yuan Lu ^a ^, ^b ^, ^c ^, ^d ^, ¹ , Jie Hua ^a ^, ^b ^, ^c ^, ^d ^, ¹ , Jiang Liu ^a ^, ^b ^, ^c ^, ^d ^, ¹ , Miao Yan Wei ^a ^, ^b ^, ^c ^, ^d , Chen Liang ^a ^, ^b ^, ^c ^, ^d , Qing Cai Meng ^a ^, ^b ^, ^c ^, ^d , Bo Zhang ^a ^, ^b ^, ^c ^, ^d , Xian Jun Yu ^a ^, ^b ^, ^c ^, ^d , Wei Wang ^a ^, ^b ^, ^c ^, ^d ^, ^* , Jin Xu ^a ^, ^b ^, ^c ^, ^d ^, ^*

Publication date (Electronic): 09 April 2022

Journal: Translational Oncology

Publisher: Neoplasia Press

Keywords: Pancreatic cancer, Paclitaxel, ceRNA, Bioinformatics analysis, Chemotherapy, TCGA, the cancer genome atlas, GEO, gene expression omnibus, GC, Genome Consortium, ssGSEA, single-sample gene set enrichment analysis, AUC, area under the curve

Read this article at

ScienceOpen Publisher PMC

Bookmark

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Highlights

•

It is the first study to focus on paclitaxel sensitivity and construct ceRNA network in pancreatic cancer.
•

We confirmed a potential PART1/hsa-mir-21/SCRN1 axis and verified it by qPCR.
•

The exploration of the prognostic signature of paclitaxel is significant to its clinical chemotherapy and immune related therapy.

Abstract

Background

Increasing numbers of studies have elucidated the role of competitive endogenous RNA (ceRNA) networks in carcinogenesis. However, the potential role of the paclitaxel-related ceRNA network in the innate mechanism and prognosis of pancreatic cancer has not been identified.

Methods

Comprehensive bioinformatics analyses were performed to identify drug-related miRNAs (DRmiRNAs), drug-related mRNAs (DRmRNAs) and drug-related lncRNAs (DRlncRNAs) and construct a ceRNA network. The ssGSEA and CIBERSORT algorithms were utilized for immune cell infiltration analysis. Additionally, we validated our paclitaxel-related ceRNA regulatory axis at the gene expression level; functional experiments were conducted to explore the biological functions of the key genes.

Results

A total of 182 mRNAs, 13 miRNAs, and 53 lncRNAs were confirmed in the paclitaxel-related ceRNA network. In total, 6 mRNAs, 4 miRNAs, and 6 lncRNAs were identified to establish a risk signature and exhibited optimal prognostic effects. The mRNA signature can predict the abundance of immune cell infiltration and the sensitivity of different chemotherapeutic drugs and may also have a guiding effect in immune checkpoint therapy. A potential PART1/hsa-mir-21/SCRN1 axis was confirmed according to the ceRNA theory and was verified by qPCR. The results indicated that PART1 knockdown markedly increased hsa-mir-21 expression but inhibited SCRN1 expression, weakening the proliferation and migration abilities.

Conclusions

We hypothesized that the paclitaxel-related ceRNA network strongly influences the innate mechanism, prognosis, and immune infiltration of pancreatic cancer. Our risk signatures can accurately predict survival outcomes and provide a clinical basis.

Related collections

Most cited references 25

Record: found
Abstract: found
Article: not found

Cancer statistics, 2020

Rebecca Siegel, Kimberly D Miller, Ahmedin Jemal (2020)

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on population-based cancer occurrence. Incidence data (through 2016) were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2017) were collected by the National Center for Health Statistics. In 2020, 1,806,590 new cancer cases and 606,520 cancer deaths are projected to occur in the United States. The cancer death rate rose until 1991, then fell continuously through 2017, resulting in an overall decline of 29% that translates into an estimated 2.9 million fewer cancer deaths than would have occurred if peak rates had persisted. This progress is driven by long-term declines in death rates for the 4 leading cancers (lung, colorectal, breast, prostate); however, over the past decade (2008-2017), reductions slowed for female breast and colorectal cancers, and halted for prostate cancer. In contrast, declines accelerated for lung cancer, from 3% annually during 2008 through 2013 to 5% during 2013 through 2017 in men and from 2% to almost 4% in women, spurring the largest ever single-year drop in overall cancer mortality of 2.2% from 2016 to 2017. Yet lung cancer still caused more deaths in 2017 than breast, prostate, colorectal, and brain cancers combined. Recent mortality declines were also dramatic for melanoma of the skin in the wake of US Food and Drug Administration approval of new therapies for metastatic disease, escalating to 7% annually during 2013 through 2017 from 1% during 2006 through 2010 in men and women aged 50 to 64 years and from 2% to 3% in those aged 20 to 49 years; annual declines of 5% to 6% in individuals aged 65 years and older are particularly striking because rates in this age group were increasing prior to 2013. It is also notable that long-term rapid increases in liver cancer mortality have attenuated in women and stabilized in men. In summary, slowing momentum for some cancers amenable to early detection is juxtaposed with notable gains for other common cancers.

0 comments Cited 9097 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language?

Leonardo Salmena, Laura Poliseno, Yvonne Tay … (2011)

Here, we present a unifying hypothesis about how messenger RNAs, transcribed pseudogenes, and long noncoding RNAs "talk" to each other using microRNA response elements (MREs) as letters of a new language. We propose that this "competing endogenous RNA" (ceRNA) activity forms a large-scale regulatory network across the transcriptome, greatly expanding the functional genetic information in the human genome and playing important roles in pathological conditions, such as cancer. Copyright © 2011 Elsevier Inc. All rights reserved.

0 comments Cited 2018 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

The multilayered complexity of ceRNA crosstalk and competition.

Yvonne Tay, John Rinn, Pier Paolo Pandolfi (2014)

Recent reports have described an intricate interplay among diverse RNA species, including protein-coding messenger RNAs and non-coding RNAs such as long non-coding RNAs, pseudogenes and circular RNAs. These RNA transcripts act as competing endogenous RNAs (ceRNAs) or natural microRNA sponges - they communicate with and co-regulate each other by competing for binding to shared microRNAs, a family of small non-coding RNAs that are important post-transcriptional regulators of gene expression. Understanding this novel RNA crosstalk will lead to significant insight into gene regulatory networks and have implications in human development and disease.

0 comments Cited 1147 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Wei Wang

Jin Xu

Journal

Journal ID (nlm-ta): Transl Oncol

Journal ID (iso-abbrev): Transl Oncol

Title: Translational Oncology

Publisher: Neoplasia Press

ISSN (Electronic): 1936-5233

Publication date PMC-release: 09 April 2022

Publication date Collection: June 2022

Publication date (Electronic): 09 April 2022

Volume: 20

Electronic Location Identifier: 101419

Affiliations

[a ]Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 Dong'An Road, Shanghai 200032, China

[b ]Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China

[c ]Shanghai Pancreatic Cancer Institute, No. 270 Dong'An Road, Shanghai 200032, China

[d ]Pancreatic Cancer Institute, Fudan University, Shanghai, China

Author notes

[* ]Corresponding authors at: Shanghai Pancreatic Cancer Institute, No. 270 Dong'An Road, Shanghai 200032, China. wangwei@ 123456fudanpci.org xujin@ 123456fudanpci.org

[1]

These authors contributed equally to this work.

Article

Publisher Item ID: S1936-5233(22)00077-8 Publisher ID: 101419

DOI: 10.1016/j.tranon.2022.101419

PMC ID: 9018166

PubMed ID: 35413498

SO-VID: fcc504ce-cd8d-4bb0-bdcc-e1e61cb41bcb

License:

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

History

Date received : 14 February 2022

Date revision received : 17 March 2022

Date accepted : 30 March 2022

Comments

Comment on this article

scite_

Cited by 2

See all cited by

Construction of a paclitaxel-related competitive endogenous RNA network and identification of a potential regulatory axis in pancreatic cancer

Read this article at

Highlights

Abstract

Background

Methods

Results

Conclusions

Related collections

RNA drug delivery

Most cited references 25

Cancer statistics, 2020

A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language?

The multilayered complexity of ceRNA crosstalk and competition.

Author and article information

Contributors

Journal

Affiliations

Author notes

Article

History

Categories

Comments

Comment on this article

Similar content 152

Cited by 2