lncRNA KCNQ1OT1 knockdown inhibits colorectal cancer cell proliferation, migration and invasiveness via thePI3K/AKT pathway

Duan,Qiaobin; Cai,Lianxu; Zheng,Kehong; Cui,Chunhui; Huang,Renli; Zheng,Zheng; Xie,Lang; Wu,Cheng; Yu,Xiang; Yu,Jinlong

doi:10.3892/ol.2020.11619

lncRNA KCNQ1OT1 knockdown inhibits colorectal cancer cell proliferation, migration and invasiveness via thePI3K/AKT pathway

Authors:
- Qiaobin Duan
- Lianxu Cai
- Kehong Zheng
- Chunhui Cui
- Renli Huang
- Zheng Zheng
- Lang Xie
- Cheng Wu
- Xiang Yu
- Jinlong Yu
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Affiliations: Department of Hernia and Abdominal Surgery, The First People's Hospital of FoShan, Affiliated FoShan Hospital of Sun Yat‑sen University, Guangdong, Foshan 528000, P.R. China, Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangdong, Guangzhou 510282, P.R. China
Published online on: May 13, 2020 https://doi.org/10.3892/ol.2020.11619
Pages: 601-610
Copyright: © Duan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Colorectal cancer (CRC) is one of the most common primary malignancies worldwide. Numerous studies have demonstrated that long non‑coding RNAs (lncRNAs) are considered as crucial regulators of tumor progression. In particular, upregulation of the lncRNA KCNQ1OT1 was reported in various types of malignancy as a promoter of tumor progression. However, the role and underlying mechanism of KCNQ1OT1 in CRC remain unclear. Thus, the present study aimed to investigate the role of KCNQ1OT1 in colorectal cancer through GEPIA, reverse transcription‑quantitative PCR (RT‑qPCR) and western blot analyses, and cell assays. GEPIA analysis demonstrated that high expression levels of KCNQ1OT1 in CRC tissues predicted a poor prognosis for patients with CRC. KCNQ1OT1 was overexpressed in CRC tissues and cell lines via RT‑qPCR analysis. Furthermore, the results from the cell viability assay, colony formation assay, wound healing assay, invasion assay and flow cytometric analysis demonstrated that KCNQ1OT1 knockdown significantly inhibited CRC cell proliferation, migration and invasiveness, and promoted CRC cell apoptosis, leading to cell cycle arrest. Western blot analysis demonstrated that KCNQ1OT1 knockdown inhibited the PI3K/AKT signaling pathway. These results suggest that KCNQ1OT1 may act as an oncogene through the PI3K/AKT signaling pathway in CRC.

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1	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI
2	Li Y, Liang L, Dai W, Cai G, Xu Y, Li X, Li Q and Cai S: Prognostic impact of programed cell death-1 (PD-1) and PD-ligand 1 (PD-L1) expression in cancer cells and tumor infiltrating lymphocytes in colorectal cancer. Mol Cancer. 15:552016. View Article : Google Scholar : PubMed/NCBI
3	Markowitz SD and Bertagnolli MM: Molecular origins of cancer: Molecular basis of colorectal cancer. N Engl J Med. 361:2449–2460. 2009. View Article : Google Scholar : PubMed/NCBI
4	ENCODE Project Consortium, . An integrated encyclopedia of DNA elements in the human genome. Nature. 489:57–74. 2012. View Article : Google Scholar : PubMed/NCBI
5	Esteller M: Non-coding RNAs in human disease. Nat Rev Genet. 12:861–874. 2011. View Article : Google Scholar : PubMed/NCBI
6	Wang KC and Chang HY: Molecular mechanisms of long noncoding RNAs. Mol Cell. 43:904–914. 2011. View Article : Google Scholar : PubMed/NCBI
7	Schmitz SU, Grote P and Herrmann BG: Mechanisms of long noncoding RNA function in development and disease. Cell Mol Life Sci. 73:2491–2509. 2016. View Article : Google Scholar : PubMed/NCBI
8	Zhang S, Ma H, Zhang D, Xie S, Wang W, Li Q, Lin Z and Wang Y: LncRNA KCNQ1OT1 regulates proliferation and cisplatin resistance in tongue cancer via miR-211-5p mediated Ezrin/Fak/Src signaling. Cell Death Dis. 9:7422018. View Article : Google Scholar : PubMed/NCBI
9	Li C, Miao R, Zhang J, Qu K and Liu C: Long non-coding RNA KCNQ1OT1 mediates the growth of hepatocellular carcinoma by functioning as a competing endogenous RNA of miR-504. Int J Oncol. 56:857–858. 2020.PubMed/NCBI
10	Feng W, Wang C, Liang C, Yang H, Chen D, Yu X, Zhao W, Geng D, Li S, Chen Z and Sun M: The dysregulated expression of KCNQ1OT1 and Its interaction with downstream factors miR-145/CCNE2 in breast cancer cells. Cell Physiol Biochem. 49:432–446. 2018. View Article : Google Scholar : PubMed/NCBI
11	NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®)-Colon Cancer v1.2019. March 15–2019
12	Tang Z, Li C, Kang B, Gao G, Li C and Zhang Z: GEPIA: A web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 45:W98–W102. 2017. View Article : Google Scholar : PubMed/NCBI
13	Wang Y, Kuang H, Xue J, Liao L, Yin F and Zhou X: LncRNA AB073614 regulates proliferation and metastasis of colorectal cancer cells via the PI3K/AKT signaling pathway. Biomed Pharmacother. 93:1230–1237. 2017. View Article : Google Scholar : PubMed/NCBI
14	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
15	Dong Z, Yang P, Qiu X, Liang S, Guan B, Yang H, Li F, Sun L, Liu H, Zou G and Zhao K: KCNQ1OT1 facilitates progression of non-small-cell lung carcinoma via modulating miRNA-27b-3p/HSP90AA1 axis. J Cell Physiol. 234:11304–11314. 2019. View Article : Google Scholar : PubMed/NCBI
16	Evan GI and Vousden KH: Proliferation, cell cycle and apoptosis in cancer. Nature. 411:342–348. 2001. View Article : Google Scholar : PubMed/NCBI
17	Huang JL, Cao SW, Ou QS, Yang B, Zheng SH, Tang J, Chen J, Hu YW, Zheng L and Wang Q: The long non-coding RNA PTTG3P promotes cell growth and metastasis via up-regulating PTTG1 and activating PI3K/AKT signaling in hepatocellular carcinoma. Mol Cancer. 17:932018. View Article : Google Scholar : PubMed/NCBI
18	Lien EC, Dibble CC and Toker A: PI3K signaling in cancer: Beyond AKT. Curr Opin Cell Biol. 45:62–71. 2017. View Article : Google Scholar : PubMed/NCBI
19	Schmitt AM and Chang HY: Long noncoding RNAs in cancer pathways. Cancer Cell. 29:452–463. 2016. View Article : Google Scholar : PubMed/NCBI
20	Chen DL, Chen LZ, Lu YX, Zhang DS, Zeng ZL, Pan ZZ, Huang P, Wang FH, Li YH, Ju HQ and Xu RH: Long noncoding RNA XIST expedites metastasis and modulates epithelial-mesenchymal transition in colorectal cancer. Cell Death Dis. 8:e30112017. View Article : Google Scholar : PubMed/NCBI
21	Han P, Li JW, Zhang BM, Lv JC, Li YM, Gu XY, Yu ZW, Jia YH, Bai XF, Li L, et al: The lncRNA CRNDE promotes colorectal cancer cell proliferation and chemoresistance via miR-181a-5p-mediated regulation of Wnt/β-catenin signaling. Mol Cancer. 16:92017. View Article : Google Scholar : PubMed/NCBI
22	Sunamura N, Ohira T, Kataoka M, Inaoka D, Tanabe H, Nakayama Y, Oshimura M and Kugoh H: Regulation of functional KCNQ1OT1 lncRNA by β-catenin. Sci Rep. 6:206902016. View Article : Google Scholar : PubMed/NCBI
23	Sun H, Li Y, Kong H, Dai S and Qian H: Dysregulation of KCNQ1OT1 promotes cholangiocarcinoma progression via miR-140-5p/SOX4 axis. Arch Biochem Biophys. 658:7–15. 2018. View Article : Google Scholar : PubMed/NCBI
24	Gong W, Zheng J, Liu X, Liu Y, Guo J, Gao Y, Tao W, Chen J, Li Z, Ma J and Xue Y: Knockdown of long non-coding RNA KCNQ1OT1 restrained glioma cells' malignancy by activating miR-370/CCNE2 axis. Front Cell Neurosci. 11:842017. View Article : Google Scholar : PubMed/NCBI
25	Huang M, Wang H, Hu X and Cao X: lncRNA MALAT1 binds chromatin remodeling subunit BRG1 to epigenetically promote inflammation-related hepatocellular carcinoma progression. Oncoimmunology. 8:e15186282018. View Article : Google Scholar : PubMed/NCBI
26	Wang Z and Qin B: Prognostic and clinicopathological significance of long noncoding RNA CTD-2510F5.4 in gastric cancer. Gastric Cancer. 22:692–704. 2019. View Article : Google Scholar : PubMed/NCBI
27	Wen J, Wang H, Dong T, Gan P, Fang H, Wu S, Li J, Zhang Y, Du R and Zhu Q: STAT3-induced upregulation of lncRNA ABHD11-AS1 promotes tumour progression in papillary thyroid carcinoma by regulating miR-1301-3p/STAT3 axis and PI3K/AKT signalling pathway. Cell Prolif. 52:e125692019. View Article : Google Scholar : PubMed/NCBI
28	Li Y, Zeng C, Hu J, Pan Y, Shan Y, Liu B and Jia L: Long non-coding RNA-SNHG7 acts as a target of miR-34a to increase GALNT7 level and regulate PI3K/Akt/mTOR pathway in colorectal cancer progression. J Hematol Oncol. 11:892018. View Article : Google Scholar : PubMed/NCBI