Suppression of small nucleolar RNA host gene 8 (SNHG8) inhibits the progression of colorectal cancer cells

Colorectal cancer (CRC) is one of the most common gastrointestinal malignancies around the world with high mortality. Accumulating evidences demonstrate that long non-coding RNAs (lncRNAs) play critical roles in CRC tumorigenesis by regulating different pathways of carcinogenesis. SNHG8 (small nucle...

Full description

Bibliographic Details
Main Authors: Md Zahirul Islam Khan, Helen Ka Wai Law
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2023-06-01
Series:Non-coding RNA Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2468054023000045
_version_ 1797868271954821120
author Md Zahirul Islam Khan
Helen Ka Wai Law
author_facet Md Zahirul Islam Khan
Helen Ka Wai Law
author_sort Md Zahirul Islam Khan
collection DOAJ
description Colorectal cancer (CRC) is one of the most common gastrointestinal malignancies around the world with high mortality. Accumulating evidences demonstrate that long non-coding RNAs (lncRNAs) play critical roles in CRC tumorigenesis by regulating different pathways of carcinogenesis. SNHG8 (small nucleolar RNA host gene 8), a lncRNA, is highly expressed in several cancers and acts as an oncogene that promotes cancer progression. However, the oncogenic role of SNHG8 in CRC carcinogenesis and the underlying molecular mechanisms remain unknown. In this study, we explored the role of SNHG8 in CRC cell lines by performing a series of functional experiments. Similar to the data reported in the Encyclopedia of RNA Interactome, our RT-qPCR results showed that SNHG8 expression was significantly upregulated in CRC cell lines (DLD-1, HT-29, HCT-116, and SW480) compared to the normal colon cell line (CCD-112CoN). We performed dicer-substrate siRNA transfection to knockdown the expression of SNHG8 in HCT-116 and SW480 cell lines which were expressing high levels of SNHG8. SNHG8 knockdown significantly reduced CRC cell growth and proliferation by inducing autophagy and apoptosis pathways through the AKT/AMPK/mTOR axis. We performed wound healing migration assay and demonstrated that SNHG8 knockdown significantly increased migration index in both cell lines, indicating reduced migration abilities of cells. Further investigation showed that SNHG8 knockdown suppresses epithelial to mesenchymal transition and reduces cellular migratory properties of CRC cells. Taken together, our study suggests that SNHG8 acts as an oncogene in CRC through the mTOR-dependent autophagy, apoptosis, and EMT pathways. Our study provides a better understanding the role of SNHG8 in CRC at molecular level and SNHG8 might be used as novel therapeutic target for CRC management.
first_indexed 2024-04-09T23:54:25Z
format Article
id doaj.art-35bff79d74c54a70b67b0dbfd70bccc6
institution Directory Open Access Journal
issn 2468-0540
language English
last_indexed 2024-04-09T23:54:25Z
publishDate 2023-06-01
publisher KeAi Communications Co., Ltd.
record_format Article
series Non-coding RNA Research
spelling doaj.art-35bff79d74c54a70b67b0dbfd70bccc62023-03-17T04:33:36ZengKeAi Communications Co., Ltd.Non-coding RNA Research2468-05402023-06-0182224232Suppression of small nucleolar RNA host gene 8 (SNHG8) inhibits the progression of colorectal cancer cellsMd Zahirul Islam Khan0Helen Ka Wai Law1Department of Health Technology and Informatics, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, ChinaCorresponding author.; Department of Health Technology and Informatics, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, ChinaColorectal cancer (CRC) is one of the most common gastrointestinal malignancies around the world with high mortality. Accumulating evidences demonstrate that long non-coding RNAs (lncRNAs) play critical roles in CRC tumorigenesis by regulating different pathways of carcinogenesis. SNHG8 (small nucleolar RNA host gene 8), a lncRNA, is highly expressed in several cancers and acts as an oncogene that promotes cancer progression. However, the oncogenic role of SNHG8 in CRC carcinogenesis and the underlying molecular mechanisms remain unknown. In this study, we explored the role of SNHG8 in CRC cell lines by performing a series of functional experiments. Similar to the data reported in the Encyclopedia of RNA Interactome, our RT-qPCR results showed that SNHG8 expression was significantly upregulated in CRC cell lines (DLD-1, HT-29, HCT-116, and SW480) compared to the normal colon cell line (CCD-112CoN). We performed dicer-substrate siRNA transfection to knockdown the expression of SNHG8 in HCT-116 and SW480 cell lines which were expressing high levels of SNHG8. SNHG8 knockdown significantly reduced CRC cell growth and proliferation by inducing autophagy and apoptosis pathways through the AKT/AMPK/mTOR axis. We performed wound healing migration assay and demonstrated that SNHG8 knockdown significantly increased migration index in both cell lines, indicating reduced migration abilities of cells. Further investigation showed that SNHG8 knockdown suppresses epithelial to mesenchymal transition and reduces cellular migratory properties of CRC cells. Taken together, our study suggests that SNHG8 acts as an oncogene in CRC through the mTOR-dependent autophagy, apoptosis, and EMT pathways. Our study provides a better understanding the role of SNHG8 in CRC at molecular level and SNHG8 might be used as novel therapeutic target for CRC management.http://www.sciencedirect.com/science/article/pii/S2468054023000045Long non-coding RNAs (lncRNAs)Small nucleolar RNA host gene 8 (SNHG8)Colorectal cancer (CRC)AutophagyApoptosisEpithelial-mesenchymal transition (EMT)
spellingShingle Md Zahirul Islam Khan
Helen Ka Wai Law
Suppression of small nucleolar RNA host gene 8 (SNHG8) inhibits the progression of colorectal cancer cells
Non-coding RNA Research
Long non-coding RNAs (lncRNAs)
Small nucleolar RNA host gene 8 (SNHG8)
Colorectal cancer (CRC)
Autophagy
Apoptosis
Epithelial-mesenchymal transition (EMT)
title Suppression of small nucleolar RNA host gene 8 (SNHG8) inhibits the progression of colorectal cancer cells
title_full Suppression of small nucleolar RNA host gene 8 (SNHG8) inhibits the progression of colorectal cancer cells
title_fullStr Suppression of small nucleolar RNA host gene 8 (SNHG8) inhibits the progression of colorectal cancer cells
title_full_unstemmed Suppression of small nucleolar RNA host gene 8 (SNHG8) inhibits the progression of colorectal cancer cells
title_short Suppression of small nucleolar RNA host gene 8 (SNHG8) inhibits the progression of colorectal cancer cells
title_sort suppression of small nucleolar rna host gene 8 snhg8 inhibits the progression of colorectal cancer cells
topic Long non-coding RNAs (lncRNAs)
Small nucleolar RNA host gene 8 (SNHG8)
Colorectal cancer (CRC)
Autophagy
Apoptosis
Epithelial-mesenchymal transition (EMT)
url http://www.sciencedirect.com/science/article/pii/S2468054023000045
work_keys_str_mv AT mdzahirulislamkhan suppressionofsmallnucleolarrnahostgene8snhg8inhibitstheprogressionofcolorectalcancercells
AT helenkawailaw suppressionofsmallnucleolarrnahostgene8snhg8inhibitstheprogressionofcolorectalcancercells