Biological functions and clinical significance of the newly identified long non‑coding RNA RP1‑85F18.6 in colorectal cancer

Ma,Yeshuo; Chen,Yifei; Lin,Changwei; Hu,Gui

doi:10.3892/or.2018.6694

Biological functions and clinical significance of the newly identified long non‑coding RNA RP1‑85F18.6 in colorectal cancer

Authors:
- Yeshuo Ma
- Yifei Chen
- Changwei Lin
- Gui Hu
View Affiliations

Affiliations: Department of Cardiology, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China, Department of Otolaryngology‑Head Neck Surgery, The Fourth Hospital of Changsha (The Changsha Affiliated Hospital of Hunan Normal University), Hunan Normal University, Changsha, Hunan 410013, P.R. China, Department of Gastrointestinal Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China, Department of Gastrointestinal Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China
Published online on: September 10, 2018 https://doi.org/10.3892/or.2018.6694
Pages: 2648-2658
Copyright: © Ma 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 biological functions of long non‑coding RNAs (lncRNAs) in cancer have not been fully elucidated. The present study demonstrated that the expression of a newly identified lncRNA, RP1‑85F18.6, was upregulated in colorectal cancer (CRC) tissues and cell lines. Knockdown of lncRNA RP1‑85F18.6 served a key role in tumor inhibition, reduced cell proliferation and invasion, disrupted the cell cycle, and increased apoptosis and pyroptosis of CRC cells. Conversely, overexpression of lncRNA RP1‑85F18.6 exerted the opposite effects. Furthermore, silencing lncRNA RP1‑85F18.6 decreased ΔNp63 expression at both the mRNA and protein levels. Furthermore, co‑transfection with ΔNp63 siRNA and lncRNA RP1‑85F18.6‑expressing vector attenuated the tumor‑promoting effects of lncRNA RP1‑85F18.6 overexpression. The expression levels of lncRNA RP1‑85F18.6, ΔNp63 and gasdermin D (GSDMD) were revealed to be associated with lymph node and distant metastases in patients with CRC, and therefore may serve as predictors in CRC. The findings of the present study suggested that lncRNA RP1‑85F18.6 may trigger CRC cell proliferation, invasion and cell cycle disruption, and suppress apoptosis and pyroptosis of CRC cells through regulating ΔNp63 expression. Therefore, lncRNA RP1‑85F18.6 and ΔNp63 may be considered unfavorable biomarkers, whereas GSDMD may be a favorable biomarker in CRC; these markers may prove valuable in the future diagnosis and prognosis of CRC.

View Figures

View References

1	Siegel RL, Miller KD, Fedewa SA, Ahnen DJ, Meester RG, Barzi A and Jemal A: Colorectal cancer statistics, 2017. CA Cancer J Clin. 67:177–193. 2017. View Article : Google Scholar : PubMed/NCBI
2	Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, Abraham J, Adair T, Aggarwal R, Ahn SY, et al: Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: A systematic analysis for the Global burden of disease study 2010. Lancet. 380:2095–2128. 2012. View Article : Google Scholar : PubMed/NCBI
3	Siegel R, Desantis C and Jemal A: Colorectal cancer statistics, 2014. CA Cancer J Clin. 64:104–117. 2014. View Article : Google Scholar : PubMed/NCBI
4	Esteller M: Non-coding RNAs in human disease. Nat Rev Genet. 12:861–874. 2011. View Article : Google Scholar : PubMed/NCBI
5	Yang Y, Junjie P, Sanjun C and Ma Y: Long non-coding RNAs in colorectal cancer: Progression and future directions. J Cancer. 8:3212–3225. 2017. View Article : Google Scholar : PubMed/NCBI
6	Deng H, Wang JM, Li M, Tang R, Tang K, Su Y, Hou Y and Zhang J: Long non-coding RNAs: New biomarkers for prognosis and diagnosis of colon cancer. Tumour Biol. 39:10104283177063322017. View Article : Google Scholar : PubMed/NCBI
7	Zhang Y, Liu X, Bai X, Lin Y, Li Z, Fu J, Li M, Zhao T, Yang H, Xu R, et al: Melatonin prevents endothelial cell pyroptosis via regulation of long noncoding RNA MEG3/miR-223/NLRP3 axis. J Pineal Res. 64:doi: 10.1111/jpi.12449. 2018. View Article : Google Scholar :
8	Chen Y, Peng Y, Fan S, Li Y, Xiao ZX and Li C: A double dealing tale of p63: An oncogene or a tumor suppressor. Cell Mol Life Sci. 75:965–973. 2018. View Article : Google Scholar : PubMed/NCBI
9	Gressner O, Schilling T, Lorenz K, Schleithoff Schulze E, Koch A, Schulze-Bergkamen H, Lena AM, Candi E, Terrinoni A, Catani MV, et al: TAp63alpha induces apoptosis by activating signaling via death receptors and mitochondria. EMBO J. 24:2458–2471. 2005. View Article : Google Scholar : PubMed/NCBI
10	Wu G, Nomoto S, Hoque MO, Dracheva T, Osada M, Lee CC, Dong SM, Guo Z, Benoit N, Cohen Y, et al: DeltaNp63alpha and TAp63alpha regulate transcription of genes with distinct biological functions in cancer and development. Cancer Res. 63:2351–2357. 2003.PubMed/NCBI
11	Srivastava K, Pickard A, McDade S and McCance DJ: p63 drives invasion in keratinocytes expressing HPV16 E6/E7 genes through regulation of Src-FAK signalling. Oncotarget. 8:16202–16219. 2017. View Article : Google Scholar : PubMed/NCBI
12	He YF, Tian DY, Yi ZJ, Yin ZK, Luo CL, Tang W and Wu XH: Upregulation of cell adhesion through delta Np63 silencing in human 5637 bladder cancer cells. Asian J Androl. 14:788–792. 2012. View Article : Google Scholar : PubMed/NCBI
13	Compagnone M, Gatti V, Presutti D, Ruberti G, Fierro C, Markert EK, Vousden KH, Zhou H, Mauriello A, Anemone L, et al: ΔNp63-mediated regulation of hyaluronic acid metabolism and signaling supports HNSCC tumorigenesis. Proc Natl Acad Sci USA. 114:13254–13259. 2017. View Article : Google Scholar : PubMed/NCBI
14	Li H, Jiang X and Niu X: Long non-coding RNA reprogramming (ROR) promotes cell proliferation in colorectal cancer via affecting P53. Med Sci Monit. 23:919–928. 2017. View Article : Google Scholar : PubMed/NCBI
15	Thorenoor N, Faltejskova-Vychytilova P, Hombach S, Mlcochova J, Kretz M, Svoboda M and Slaby O: Long non-coding RNA ZFAS1 interacts with CDK1 and is involved in p53-dependent cell cycle control and apoptosis in colorectal cancer. Oncotarget. 7:622–637. 2016. View Article : Google Scholar : PubMed/NCBI
16	Li XL, Subramanian M, Jones MF, Chaudhary R, Singh DK, Zong X, Gryder B, Sindri S, Mo M, Schetter A, et al: Long noncoding RNA PURPL suppresses basal p53 levels and promotes tumorigenicity in colorectal cancer. Cell Rep. 20:2408–2423. 2017. View Article : Google Scholar : PubMed/NCBI
17	Edge SB and Compton CC: The American Joint Committee on cancer: The 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 17:1471–1474. 2010. View Article : Google Scholar : PubMed/NCBI
18	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2^−ΔΔCT method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
19	Yun DP, Wang YQ, Meng DL, Ji YY, Chen JX, Chen HY and Lu DR: Actin-capping protein CapG is associated with prognosis, proliferation and metastasis in human glioma. Oncol Rep. 39:1011–1022. 2018.PubMed/NCBI
20	Xie S, Ge Q, Wang X, Sun X and Kang Y: Long non-coding RNA ZFAS1 sponges miR-484 to promote cell proliferation and invasion in colorectal cancer. Cell Cycle. 17:154–161. 2018. View Article : Google Scholar : PubMed/NCBI
21	Chen Y, Zhang Y, He J, Fu Y, Lin C and Li X: MicroRNA-133b is regulated by TAp63 while no gene mutation is present in colorectal cancer. Oncol Rep. 37:1646–1652. 2017. View Article : Google Scholar : PubMed/NCBI
22	Wu H, Wu R, Chen M, Li D, Dai J, Zhang Y, Gao K, Yu J, Hu G, Guo Y, et al: Comprehensive analysis of differentially expressed profiles of lncRNAs and construction of miR-133b mediated ceRNA network in colorectal cancer. Oncotarget. 8:21095–21105. 2017.PubMed/NCBI
23	Li J, Ma W, Zeng P, Wang J, Geng B, Yang J and Cui Q: LncTar: A tool for predicting the RNA targets of long noncoding RNAs. Brief Bioinform. 16:806–812. 2015. View Article : Google Scholar : PubMed/NCBI
24	Shi J, Zhao Y, Wang K, Shi X, Wang Y, Huang H, Zhuang Y, Cai T, Wang F and Shao F: Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature. 526:660–665. 2015. View Article : Google Scholar : PubMed/NCBI
25	Ding J, Wang K, Liu W, She Y, Sun Q, Shi J, Sun H, Wang DC and Shao F: Pore-forming activity and structural autoinhibition of the gasdermin family. Nature. 535:111–116. 2016. View Article : Google Scholar : PubMed/NCBI
26	Shi J, Gao W and Shao F: Pyroptosis: Gasdermin-mediated programmed necrotic cell death. Trends Biochem Sci. 42:245–254. 2017. View Article : Google Scholar : PubMed/NCBI
27	Chen DL, Lu YX, Zhang JX, Wei XL, Wang F, Zeng ZL, Pan ZZ, Yuan YF, Wang FH, Pelicano H, et al: Long non-coding RNA UICLM promotes colorectal cancer liver metastasis by acting as a ceRNA for microRNA-215 to regulate ZEB2 expression. Theranostics. 7:4836–4849. 2017. View Article : Google Scholar : PubMed/NCBI
28	Zhang J, Li Z, Liu L, Wang Q, Li S, Chen D, Hu Z, Yu T, Ding J, Li J, et al: Long noncoding RNA TSLNC8 is a tumor suppressor that inactivates the interleukin-6/STAT3 signaling pathway. Hepatology. 67:171–187. 2018. View Article : Google Scholar : PubMed/NCBI
29	Wu Q, Deng J, Fan D, Duan Z, Zhu C, Fu R and Wang S: Ginsenoside Rh4 induces apoptosis and autophagic cell death through activation of the ROS/JNK/p53 pathway in colorectal cancer cells. Biochem Pharmacol. 148:64–74. 2017. View Article : Google Scholar : PubMed/NCBI
30	Liu K, Yao H, Lei S, Xiong L, Qi H, Qian K, Liu J, Wang P and Zhao H: The miR-124-p63 feedback loop modulates colorectal cancer growth. Oncotarget. 8:29101–29115. 2017.PubMed/NCBI
31	Nayak KB, Kuila N, Das Mohapatra A, Panda AK and Chakraborty S: EVI1 targets ΔNp63 and upregulates the cyclin dependent kinase inhibitor p21 independent of p53 to delay cell cycle progression and cell proliferation in colon cancer cells. Int J Biochem Cell Biol. 45:1568–1576. 2013. View Article : Google Scholar : PubMed/NCBI
32	Balboni AL, Cherukuri P, Ung M, DeCastro AJ, Cheng C and DiRenzo J: p53 and ΔNp63α coregulate the transcriptional and cellular response to TGFβ and BMP signals. Mol Cancer Res. 13:732–742. 2015. View Article : Google Scholar : PubMed/NCBI
33	He Y, Wu X, Tang W, Tian D, Luo C, Yin Z and Du H: Impaired delta NP63 expression is associated with poor tumor development in transitional cell carcinoma of the bladder. J Korean Med Sci. 23:825–832. 2008. View Article : Google Scholar : PubMed/NCBI
34	Giacobbe A, Compagnone M, Bongiorno-Borbone L, Antonov A, Markert EK, Zhou JH, Annicchiarico-Petruzzelli M, Melino G and Peschiaroli A: p63 controls cell migration and invasion by transcriptional regulation of MTSS1. Oncogene. 35:1602–1608. 2016. View Article : Google Scholar : PubMed/NCBI
35	Wang Y, Gao W, Shi X, Ding J, Liu W, He H, Wang K and Shao F: Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin. Nature. 547:99–103. 2017. View Article : Google Scholar : PubMed/NCBI
36	Thomas DS, Fourkala EO, Apostolidou S, Gunu R, Ryan A, Jacobs I, Menon U, Alderton W, Gentry-Maharaj A and Timms JF: Evaluation of serum CEA, CYFRA21-1 and CA125 for the early detection of colorectal cancer using longitudinal preclinical samples. Br J Cancer. 113:268–274. 2015. View Article : Google Scholar : PubMed/NCBI
37	Gao Y, Wang J, Zhou Y, Sheng S, Qian SY and Huo X: Evaluation of serum CEA, CA19-9, CA72-4, CA125 and ferritin as diagnostic markers and factors of clinical parameters for colorectal cancer. Sci Rep. 8:27322018. View Article : Google Scholar : PubMed/NCBI