Long noncoding RNA SNHG1 promotes cell proliferation through PI3K/AKT signaling pathway in pancreatic ductal adenocarcinoma

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.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most common causes of cancer-related death. Recently, long noncoding RNAs (lncRNAs) have emerged as significant regulators in numerous cancers, including PDAC. LncRNA small nucleolar RNA host gene 1 (SNHG1) has been reported in the development of several tumors, but the biological roles of it in PDAC remain to be illuminated. This study aims to investigate the function of lncRNA SNHG1, revealing its molecular mechanism and clinical significance in PDAC. Herein, we found that SNHG1 was highly expressed in PDAC tissues in comparison with adjacent noncancerous tissues, being closely related to tumor size and TNM stage. Functionally, silencing of SNHG1 could significantly inhibit cell proliferation, promote cell apoptosis, as well as alter cell cycle progression, whereas the contrary results could be presented in the overexpression of SNHG1. In addition, in vivo xenograft experiment also further confirmed the above results. Finally, an activator (740Y-P) and inhibitor (LY294002) of the PI3K/AKT signaling pathway were used in the western blot assays and the following rescue experiments, demonstrating that SNHG1 facilitates cell proliferation and tumorigenicity partly via the PI3K/AKT signaling pathway in PDAC. Hence, SNHG1 may be a prospective therapeutic target.

Related collections

Most cited references 17

Record: found
Abstract: found
Article: found

Is Open Access

The long non-coding RNA HOTTIP promotes progression and gemcitabine resistance by regulating HOXA13 in pancreatic cancer

Zhihua Li, Xiaohui Zhao, Yu-bo Zhou … (2015)

Background The human genome encodes many long non-coding RNAs (lncRNAs). However, their biological functions, molecular mechanisms, and the prognostic value associated with pancreatic ductal adenocarcinoma (PDAC) remain to be elucidated. Here, we identify a fundamental role for the lncRNA HOXA transcript at the distal tip (HOTTIP) in the progression and chemoresistance of PDAC. Methods High-throughput microarrays were performed to detect the expression profiles of lncRNAs and messenger RNAs in eight human PDAC tissues and four pancreatic tissues. Quantitative real-time PCR was used to determine the levels of HOTTIP and HOXA13 transcripts in PDAC cell lines and 90 PDAC samples from patients. HPDE6 cells (immortalized human pancreatic ductal epithelial cells) and corresponding adjacent non-neoplastic tissues were used as controls, respectively. The functions of HOTTIP and HOXA13 in cell proliferation, invasion, and epithelial-mesenchymal transition were evaluated by targeted knockdown in vitro. CCK-8 assays, colony formation assays, and xenografts in nude mice were used to investigate whether targeted silencing of HOTTIP could sensitize pancreatic cancer cells to gemcitabine. Immunohistochemistry was performed to investigate the relationship between HOXA13 expression and patient outcome. Results Microarray analyses revealed that HOTTIP was one of the most significantly upregulated lncRNAs in PDAC tissues compared with pancreatic tissues. Quantitative PCR further verified that HOTTIP levels were increased in PDAC cell lines and patient samples compared with controls. Functionally, HOTTIP silencing resulted in proliferation arrest by altering cell-cycle progression, and impaired cell invasion by inhibiting epithelial-mesenchymal transition in pancreatic cancer. Additionally, inhibition of HOTTIP potentiated the antitumor effects of gemcitabine in vitro and in vivo. Furthermore, knockdown of HOXA13 by RNA interference (siHOXA13) revealed that HOTTIP promoted PDAC cell proliferation, invasion, and chemoresistance, at least partly through regulating HOXA13. Immunohistochemistry results revealed that higher HOXA13 expression was correlated with lymph node metastasis, poor histological differentiation, and decreased overall survival in PDAC patients. Conclusions As a crucial tumor promoter, HOTTIP promotes cell proliferation, invasion, and chemoresistance by modulating HOXA13. Therefore, the HOTTIP/HOXA13 axis is a potential therapeutic target and molecular biomarker for PDAC. Electronic supplementary material The online version of this article (doi:10.1186/s12967-015-0442-z) contains supplementary material, which is available to authorized users.

0 comments Cited 108 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Analysis of mortality rates for pancreatic cancer across the world

D Hariharan, A. Saied, H.M. Kocher (2008)

Pancreas cancer is the fourth commonest cause of cancer-related mortality across the world, with incidence equalling mortality. A recent study has suggested that both the incidence and the mortality of pancreatic cancer are falling in the UK. We investigated whether this trend was being seen all over the world. Age-standardized mortality (world) rates [ASR(W)] for pancreatic cancer were extracted separately for males and females from a database maintained by the International Agency for Research on Cancer for 51 countries across the world (Europe, 33 countries; Americas, 8 countries; and Asia, 10 countries) for the period 1992-2002; log-linear regression analysis was performed to analyse trends in the past decade. In the period 1992-2002, the ASR(W) remained static across most countries for both sexes. The highest mortality rates (for both sexes) were seen in Central Europe [range: men (8-12), women (4.5-7)] with trends towards increasing mortality in Romania (p<0.001), along with Albania, Spain and Croatia (p<0.01). Korea in the Far East, too, demonstrated increasing mortality trends for both sexes (men p<0.001, women p<0.01). Increasing mortality trends were also observed among women in France (p<0.001). In Canada, there was a decline in mortality [men (7.5-6.4), women (5.9-5); p<0.01], while for men there was a downward trend in Ireland, the UK, Switzerland, Austria, and Poland [p<0.05]. The changes perhaps reflect standardization and consolidation of diagnostic tests for pancreatic cancer in the Western world and further in-depth analysis would be required.

0 comments Cited 105 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

SNHG1 lncRNA negatively regulates miR-199a-3p to enhance CDK7 expression and promote cell proliferation in prostate cancer.

Jianping Li, Zhipeng Zhang, Li Xiong … (2017)

Long noncoding RNAs (lncRNAs) have been reported to play vital roles in the development of human cancers, but our understandings of most lncRNAs in cancers are still limited. Recently, accumlating evidences have showed that many RNA transcripts could function as competing endogenous RNAs (ceRNAs) by competitively binding common microRNAs. In this study, we demonstrated that a lncRNA, Small Nucleolar RNA Host Gene 1 (SNHG1), as a ceRNA for miR-199a-3p, played a critical role in prostate cancer cell proliferation. We found that SNHG1 was aberrantly up-regulated in prostate carcinoma tissues; while, miR-199a-3p was abnormally down-regulated. The level of SNHG1 in prostate cancer was significantly negatively correlated with that of miR-199a-3p. Our data indicated that SNHG1 could interact with miR-199a-3p and inhibit the activity of miR-199a-3p in prostate cancer cells. In addition, miR-199a-3p could target the 3' UTR of CDK7 and suppress CDK7 expression. More importantly, SNHG1 increased CDK7 expression by competitively binding miR-199a-3p, and then promoted cell proliferation and cell cycle progression in prostate cancer. Taken together, these findings elucidated a novel mechanism of prostate cancer progression. Thus, SNHG1 might serve as a potential target for prostate cancer therapies.

0 comments Cited 58 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): J Cancer

Journal ID (iso-abbrev): J Cancer

Journal ID (publisher-id): jca

Title: Journal of Cancer

Publisher: Ivyspring International Publisher (Sydney )

ISSN (Electronic): 1837-9664

Publication date Collection: 2018

Publication date (Electronic): 23 June 2018

Volume: 9

Issue: 15

Pages: 2713-2722

Affiliations

[1 ]Department of General Surgery, Tongji hospital, Tongji University School of Medicine, Shanghai 200065, China.

[2 ]Department of Pancreas and Hepatobiliary Surgery, Pancreas Cancer Institute, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.

[3 ]Department of General Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.

Author notes

✉ Corresponding author: Kaixing Ai, Department of General Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No.507 Zhengmin Road, Shanghai 200433, China. E-mail: akxing8258@ 123456tongji.edu.cn

Competing Interests: The authors have declared that no competing interest exists.

Article

Publisher ID: jcav09p2713

DOI: 10.7150/jca.26207

PMC ID: 6072808

PubMed ID: 30087712

SO-VID: 54d92772-ffbd-4fad-8694-5121e4f37cee

License:

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.

Long noncoding RNA SNHG1 promotes cell proliferation through PI3K/AKT signaling pathway in pancreatic ductal adenocarcinoma

Read this article at

Abstract

Related collections

Karger: Dermatology

Most cited references 17

The long non-coding RNA HOTTIP promotes progression and gemcitabine resistance by regulating HOXA13 in pancreatic cancer

Analysis of mortality rates for pancreatic cancer across the world

SNHG1 lncRNA negatively regulates miR-199a-3p to enhance CDK7 expression and promote cell proliferation in prostate cancer.

Author and article information

Journal

Affiliations

Author notes

Article

History

Categories

Comments

Comment on this article

Similar content 857

Cited by 22

Most referenced authors 603