Wang F, Mu HF, Wang C, Tang Y, Si MY, Peng J. LncRNA PCAT6 promotes progression and metastasis of colonic neuroendocrine carcinoma via MAPK pathway. World J Gastrointest Oncol 2025; 17(2): 96230 [DOI: 10.4251/wjgo.v17.i2.96230]
Corresponding Author of This Article
Jing Peng, MM, Department of General Surgery, Nanjing Tongren Hospital, No. 2007 Jiyin Avenue, Jiangning District, Nanjing 211100, Jiangsu Province, China. pengjingwxn@163.com
Research Domain of This Article
Biology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Fei Wang, Hai-Feng Mu, Chun Wang, Yue Tang, Jing Peng, Department of General Surgery, Nanjing Tongren Hospital, Nanjing 211100, Jiangsu Province, China
Ming-Yuan Si, Department of Pathology, Nanjing Tongren Hospital, Nanjing 211100, Jiangsu Province, China
Co-first authors: Fei Wang and Hai-Feng Mu.
Author contributions: Wang F and Mu HF conceived and designed the experiments; Wang F, Mu HF, Wang C, Tang Y, Si MY and Peng J carried out the experiments; Wang F, Mu HF and Peng J analyzed the data, drafted the manuscript. All authors agreed to be accountable for all aspects of the work. All authors have read and approved the final manuscript.
Institutional review board statement: Our study was approved by the Ethics Committee of Nanjing Tongren Hospital (2022-03-016). All patients had signed an informed consent before the study.
Institutional animal care and use committee statement: All animal experiments were reviewed and approved by the Ethics Review Committee of Southeast University (20210701004) and were performed in strict accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals.
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jing Peng, MM, Department of General Surgery, Nanjing Tongren Hospital, No. 2007 Jiyin Avenue, Jiangning District, Nanjing 211100, Jiangsu Province, China. pengjingwxn@163.com
Received: April 30, 2024 Revised: September 18, 2024 Accepted: December 2, 2024 Published online: February 15, 2025 Processing time: 263 Days and 2 Hours
Abstract
BACKGROUND
Colonic neuroendocrine carcinomas (NECs) are highly malignant and invasive with poor prognosis. Long noncoding RNAs (LncRNAs) participate in the tumorigenesis and metastasis of multiple cancers
AIM
To detect the roles and mechanisms of lncRNA prostate cancer associated transcript 6 (PCAT6) in the progression of colonic NEC.
METHODS
Human NEC and adjacent normal samples were collected for immunohistochemistry staining of CgA and real-time quantitative polymerase chain reaction (RT-qPCR) of PCAT6 mRNA level. Subcutaneous xenograft tumor model and lung metastasis model were established in nude mice. The lung tissues were stained by hematoxylin and eosin to assess pulmonary metastasis. The expression of epithelial-mesenchymal transition (EMT)-related markers and pathway-related genes was measured by RT-qPCR and western blotting. CD56 expression was assessed by immunofluorescence staining. The biological functions of PCAT6 were examined by cell counting kit-8, colony formation assays, Transwell assays and wound healing assays. The interaction between PCAT6 and its potential downstream target was verified by luciferase reporter assays.
RESULTS
LncRNA PCAT6 was upregulated in human NEC samples and LCC-18 cells, and its high expression was positively correlated with poor prognosis in patients with colonic NEC. Additionally, the expression of PCAT6 was positively associated with the proliferation, migration, invasion, and EMT of LCC-18 cells. Moreover, PCAT6 facilitated tumor growth, lung metastasis and EMT in xenografts. Mechanistically, PCAT6 promoted the activation of MAPK to enhance the EMT in colonic NEC by targeting miR-326.
CONCLUSION
In conclusion, lncRNA PCAT6 accelerates the process of colonic NEC by activating ERK/p38 MAPK signaling through targeting miR-326. These results might provide useful information for exploring the potential therapeutic targets in colonic NEC.
Core Tip: Prostate cancer associated transcript 6 (PCAT6) is highly expressed in neuroendocrine carcinomas (NECs) tissues and cells PCAT6 promotes the proliferation, migration and invasion of NEC cells PCAT6 facilitates tumor growth and lung metastasis in vivo PCAT6 enhances the epithelial-mesenchymal transition (EMT) in NECPCAT6 promotes the activation of MAPK to enhance the EMT in NEC.
