LncRNA SNHG6 inhibits cell proliferation and metastasis by targeting ETS1 via the PI3K/AKT/mTOR pathway in colorectal cancer

Meng,Su; Jian,Zhao; Yan,Xiaofei; Li,Jibin; Zhang,Rui

doi:10.3892/mmr.2019.10510

LncRNA SNHG6 inhibits cell proliferation and metastasis by targeting ETS1 via the PI3K/AKT/mTOR pathway in colorectal cancer

Authors:
- Su Meng
- Zhao Jian
- Xiaofei Yan
- Jibin Li
- Rui Zhang
View Affiliations

Affiliations: Department of Medical Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110042, P.R. China
Published online on: July 19, 2019 https://doi.org/10.3892/mmr.2019.10510
Pages: 2541-2548
Copyright: © Meng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The term ‘long non‑coding RNAs’ (lncRNAs) refers to all non‑protein coding transcripts >200 nucleotides in length. Dysregulation of lncRNAs has been identified in colorectal cancer, which is one of the more serious types of cancer worldwide, third place in the mortality rates, and is associated with poor prognoses. Novel evidence suggests that lncRNAs serve an important role in regulating the development and progression of colorectal cancer. In the present study, it was demonstrated that SNHG6 expression was downregulated in colorectal cancer tissues by reverse transcription quantitative polymerase chain reaction assays; however, ETS1 expression levels were upregulated. Overexpression of SNHG6 not only inhibited the proliferation of colon cancer cells in vitro by inducing apoptosis, but also inhibited cell proliferation, invasion and migration. The overexpression of SNHG6 inhibited colon cell viability and proliferation by targeting ETS1 through the phosphoinositide 3‑kinase/protein kinase B/mechanistic target of rapamycin signaling pathway. These results suggested that SNHG6 may directly suppress ETS1, which may be one of potential mechanisms through which it inhibits the viability and proliferation of colorectal cancer cells, and it provides novel insight into the carcinogenesis of colorectal cancer. In addition, it may assist in the development of a treatment approach for ETS1‑activated colorectal cancer.

View Figures

View References

1	Jones P, Cade JE, Evans CEL, Hancock N and Greenwood DC: Does adherence to the World Cancer Research Fund/American Institute of Cancer Research cancer prevention guidelines reduce risk of colorectal cancer in the UK Women's cohort study? Br J Nutr. 119:340–348. 2018. View Article : Google Scholar : PubMed/NCBI
2	van der Werf A, Arthey K, Hiesmayr M, Sulz I, Schindler K, Laviano A, Langius J and de van der Schueren M: The determinants of reduced dietary intake in hospitalised colorectal cancer patients. Support Care Cancer. 26:2029–2047. 2018. View Article : Google Scholar
3	Han J, Hur H, Min BS, Lee KY and Kim NK: Predictive factors for lymph node metastasis in submucosal invasive colorectal carcinoma: A new proposal of depth of invasion for radical surgery. World J Surg. 42:2635–2641. 2018. View Article : Google Scholar : PubMed/NCBI
4	Souza BU, Souza NCS, Martucci RB, Rodrigues VD, Pinho NB, Gonzalez MC and Avesani CM: Factors associated with sarcopenia in patients with colorectal cancer. Nutr Cancer. 70:176–183. 2018. View Article : Google Scholar : PubMed/NCBI
5	Woodall M and DeLetter M: Colorectal cancer: A collaborative approach to improve education and screening in a rural population. Clin J Oncol Nurs. 22:69–75. 2018. View Article : Google Scholar : PubMed/NCBI
6	Ruiz-Tovar J, Llavero C, Morales V and Gamallo C: Effect of the application of a bundle of three measures (intraperitoneal lavage with antibiotic solution, fascial closure with triclosan-coated sutures and mupirocin ointment application on the skin staples) on the surgical site infection after elective laparoscopic colorectal cancer surgery. Surg Endosc. 32:3495–3501. 2018. View Article : Google Scholar : PubMed/NCBI
7	Wu W, Yan S, Liao X, Xiao H, Fu Z, Chen L, Mou J, Yu H, Zhao L and Liu X: Curative versus palliative treatments for colorectal cancer with peritoneal carcinomatosis: A systematic review and meta-analysis. Oncotarget. 8:113202–113212. 2017. View Article : Google Scholar : PubMed/NCBI
8	Vayrynen JP, Tuomisto A, Vayrynen SA, Klintrup K, Karhu T, Mäkelä J, Herzig KH, Karttunen TJ and Mäkinen MJ: Preoperative anemia in colorectal cancer: Relationships with tumor characteristics, systemic inflammation, and survival. Sci Rep. 8:11262018. View Article : Google Scholar : PubMed/NCBI
9	Yan K, Tian J, Shi W, Xia H and Zhu Y: LncRNA SNHG6 is associated with poor prognosis of gastric cancer and promotes cell proliferation and EMT through epigenetically silencing p27 and sponging miR-101-3p. Cell Physiol Biochem. 42:999–1012. 2017. View Article : Google Scholar : PubMed/NCBI
10	Birgani MT, Hajjari M, Shahrisa A, Khoshnevisan A, Shoja Z, Motahari P and Farhangi B: Long non-coding RNA SNHG6 as a potential biomarker for hepatocellular carcinoma. Pathol Oncol Res. 24:329–337. 2017. View Article : Google Scholar : PubMed/NCBI
11	Cao C, Zhang T, Zhang D, Xie L, Zou X, Lei L, Wu D and Liu L: The long non-coding RNA, SNHG6-003, functions as a competing endogenous RNA to promote the progression of hepatocellular carcinoma. Oncogene. 36:1112–1122. 2017. View Article : Google Scholar : PubMed/NCBI
12	Cao B, Tan S, Tang H, Chen Y and Shu P: miR5125p suppresses proliferation, migration and invasion, and induces apoptosis in nonsmall cell lung cancer cells by targeting ETS1. Mol Med Rep. 19:3604–3614. 2019.PubMed/NCBI
13	Conrad S, Demurger F, Moradkhani K, Pichon O, Le Caignec C, Pascal C, Thomas C, Bayart S, Perlat A, Dubourg C, et al: 11q24.2q24.3 microdeletion in two families presenting features of jacobsen syndrome, without intellectual disability: Role of FLI1, ETS1, and SENCR long noncoding RNA. Am J Med Genet A. 179-993-1000. 2019. View Article : Google Scholar : PubMed/NCBI
14	Shen C, Yin Y, Chen H, Tang S, Yin X, Zhou Z, Zhang B and Chen Z: Neuroendocrine tumors of colon and rectum: Validation of clinical and prognostic values of the World Health Organization 2010 grading classifications and european neuroendocrine tumor society staging systems. Oncotarget. 8:22123–22134. 2017.PubMed/NCBI
15	Expert Panel on Gastrointestinal Imaging, ; Fowler KJ, Kaur H, Cash BD, Feig BW, Gage KL, Garcia EM, Hara AK, Herman JM, Kim DH, et al: ACR appropriateness criteria((R)) pretreatment staging of colorectal cancer. J Am Coll Radiol. 14:S234–S244. 2017. View Article : Google Scholar : PubMed/NCBI
16	Ogawa T, Hirohashi Y, Murai A, Nishidate T, Okita K, Wang L, Ikehara Y, Satoyoshi T, Usui A, Kubo T, et al: ST6GALNAC1 plays important roles in enhancing cancer stem phenotypes of colorectal cancer via the Akt pathway. Oncotarget. 8:112550–112564. 2017. View Article : Google Scholar : PubMed/NCBI
17	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
18	Luan A, Hu MS, Leavitt T, Brett EA, Wang KC, Longaker MT and Wan DC: Noncoding RNAs in Wound Healing: A new and vast frontier. Adv Wound Care (New Rochelle). 7:19–27. 2018. View Article : Google Scholar : PubMed/NCBI
19	Sallam T, Sandhu J and Tontonoz P: Long noncoding RNA discovery in cardiovascular disease: Decoding form to function. Circ Res. 122:155–166. 2018. View Article : Google Scholar : PubMed/NCBI
20	Chen S, Zhu J, Wang F, Guan Z, Ge Y, Yang X and Cai J: LncRNAs and their role in cancer stem cells. Oncotarget. 8:110685–110692. 2017.PubMed/NCBI
21	Malhotra A, Jain M, Prakash H, Vasquez KM and Jain A: The regulatory roles of long non-coding RNAs in the development of chemoresistance in breast cancer. Oncotarget. 8:110671–110684. 2017. View Article : Google Scholar : PubMed/NCBI
22	Lv P, Qiu X, Gu Y, Yang X, Xu X and Yang Y: Long non-coding RNA SNHG6 enhances cell proliferation, migration and invasion by regulating miR-26a-5p/MAPK6 in breast cancer. Biomed Pharmacother. 110:294–301. 2019. View Article : Google Scholar : PubMed/NCBI
23	Li Y, Li D, Zhao M, Huang S, Zhang Q, Lin H, Wang W, Li K, Li Z, Huang W, et al: Long noncoding RNA SNHG6 regulates p21 expression via activation of the JNK pathway and regulation of EZH2 in gastric cancer cells. Life Sci. 208:295–304. 2018. View Article : Google Scholar : PubMed/NCBI
24	Zhang Y, Li R, Ding X, Zhang K and Qin W: Upregulation of long non-coding RNA SNHG6 promote esophageal squamous cell carcinoma cell malignancy and its diagnostic value. Am J Transl Res. 11:1084–1091. 2019.PubMed/NCBI