Genome-wide CRISPR-Cas9 screening identifies that hypoxia-inducible factor-1a-induced CBX8 transcription promotes pancreatic cancer progression via IRS1/AKT axis

doi:10.4251/wjgo.v13.i11.1709

Advanced Search

BPG is committed to discovery and dissemination of knowledge

Home / Archive / Volume 13, Issue 11

This Article

Peer-Review Report of This Article

CrossCheck and Google Search of This Article

Academic Rules and Norms of This Article

Citation of this article

Corresponding Author of This Article

Research Domain of This Article

Article-Type of This Article

Open-Access Policy of This Article

Times Cited Counts in Google of This Article

Number of Hits and Downloads for This Article

Total Article Views (5839)

All Articles published online

The chart showing PDF series, WORD series, HTML series, Figures (1-6) series.

Item

Count

PDF

341

WORD

HTML

3159

Figures (1-6)

480

Sum=4069

Publishing Process of This Article

The chart showing Browse series, Download series.

Item

Count

Browse

540

Download

1235

Sum=1775

Nov 15, 2021 (publication date) through Feb 23, 2026

Times Cited of This Article

Times Cited (9)

Journal Information of This Article

Publication Name

World Journal of Gastrointestinal Oncology

ISSN

1948-5204

Publisher of This Article

Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

- Full Article with Cover (PDF)
- Full Article (XML)

Basic Study

World J Gastrointest Oncol. Nov 15, 2021; 13(11): 1709-1724
Published online Nov 15, 2021. doi: 10.4251/wjgo.v13.i11.1709

Genome-wide CRISPR-Cas9 screening identifies that hypoxia-inducible factor-1a-induced CBX8 transcription promotes pancreatic cancer progression via IRS1/AKT axis

Bu-Wei Teng, Kun-Dong Zhang, Yu-Han Yang, Zeng-Ya Guo, Wei-Wei Chen, Zheng-Jun Qiu

Bu-Wei Teng, Zheng-Jun Qiu, Shanghai General Hospital of Nanjing Medical University, 100 Haining Road, Shanghai 200080, China

Bu-Wei Teng, Lianyungang Clinical College of Nanjing Medical University/The First People’s Hospital of Lianyungang, 6 Zhenhua East Road, Haizhou District, City of Lianyungang, Jiangsu Province 222061, China

Kun-Dong Zhang, Yu-Han Yang, Zeng-Ya Guo, Wei-Wei Chen, Department of General Surgery, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai 200080, China

Author contributions: Qiu ZJ and Teng BW conceived and supervised the study; Teng BW performed most of the experiments and data analysis; Zhang KD performed most functional experiments and data analysis; Qiu ZJ and Teng BW wrote the manuscript; Yang YH, Guo ZY, and Chen WW took part in the discussions; all the authors discussed the results and commented on the manuscript, and approved the final version.

Supported by National Natural Science Foundation of China (General Program), No. 81974372 (to Qiu ZJ).

Institutional review board statement: The study was reviewed and approved by the Shanghai General Hospital Institutional Review Board (Approval No. 2020KY083).

Conflict-of-interest statement: The authors declare no conflicts of interest for this work.

Data sharing statement: No additional data are available.

Corresponding author: Zheng-Jun Qiu, MD, Chief Doctor, Director, Surgeon, Shanghai General Hospital of Nanjing Medical University; Department of General Surgery, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, No. 100 Haining Road, Shanghai 201600, China. qiuzjdoctor@sina.com

Received: April 14, 2021
Peer-review started: April 20, 2021
First decision: June 23, 2021
Revised: June 24, 2021
Accepted: August 23, 2021
Article in press: August 23, 2021
Published online: November 15, 2021
Processing time: 212 Days and 5.9 Hours

ARTICLE HIGHLIGHTS

Research background

Pancreatic cancer (PC) is one of the most lethal cancers worldwide. It has become the second most fatal cancer in the United States. Chromobox (CBX)8 promotes tumor growth and metastasis in other cancers. However, whether CBX8 is involved in the proliferation of PC cells remains unknown.

Research motivation

Many studies have shown that the prognosis of patients with PC remains poor after complete surgical resection. Therefore, it is important to study the occurrence and development of PC and the corresponding targeted therapy. We hope to provide a novel therapeutic target for patients with PC.

Research objectives

The present study aimed to investigate the function of the CBX8/IRS1/AKT axis in PC.

Research methods

Genome-wide CRISPR-Cas9 screening was performed to select genes that could facilitate PC cell proliferation. A total of 244 candidate genes were identified as being responsible for proliferation of PC cells using deep single guide RNA sequencing. Quantitative reverse transcription-polymerase chain reaction was used to detect the expression of CBX8 in PC tissues and cells. The regulatory roles of CBX8 in cell proliferation, migration, and invasion were verified by CCK-8 and Transwell assays.

Research results

CBX8 was upregulated in pancreatic tumor tissues and shown to drive PC cell proliferation. Higher expression of CBX8 was correlated with worse outcomes of PC patients from two independent cohorts with a total of 116 cases. CBX8 also served as a promising therapeutic target for a PC xenograft model. We demonstrated that HIF-1a induced CBX8 transcription by binding to the promoter of CBX8. CBX8 efficiently activated the PI3K/AKT signaling pathway by upregulating insulin receptor substrate (IRS)1.

Research conclusions

CBX8 promotes PC cell progression by activating the IRS1/AKT pathway.

Research perspectives

CBX8 could promote PC progression, which might provide a potential treatment strategy for this malignancy.