Long noncoding RNA LINC00649 functions as a microRNA‑432‑5p sponge to facilitate tumourigenesis in colorectal cancer by upregulating HDGF

Bao,Junjie; Bi,Xiaokai; Wang,Jingbo; Li,Xiaoqiang

doi:10.3892/mmr.2022.12620

Long noncoding RNA LINC00649 functions as a microRNA‑432‑5p sponge to facilitate tumourigenesis in colorectal cancer by upregulating HDGF

Authors:
- Junjie Bao
- Xiaokai Bi
- Jingbo Wang
- Xiaoqiang Li
View Affiliations

Affiliations: Department of General Surgery, The First People's Hospital of Chongqing Liangjiang, Chongqing 401121, P.R. China
Published online on: January 26, 2022 https://doi.org/10.3892/mmr.2022.12620
Article Number: 104
Copyright: © Bao 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

Long intergenic nonprotein coding RNA 649 (LINC00649) is a functional regulator in acute myeloid leukaemia. However, the contribution of LINC00649 in colorectal cancer (CRC) has yet to be confirmed. Accordingly, the present investigation was devoted to exploring the detailed functions of LINC00649 and reveal the mechanisms underlying the LINC00649‑induced promotion of CRC progression. LINC00649 expression in CRC was investigated by reverse transcription‑quantitative PCR. Knockdown of LINC00649 was achieved using small interfering RNAs or short hairpin RNA, followed by functional experiments. The binding between LINC00649 and microRNA (miR)‑432‑5p was predicted by a bioinformatics tool, and corroborated by luciferase reporter assay and RNA immunoprecipitation. In the present study, LINC00649 was expressed at a high level in CRC. The aberrant expression of LINC00649 exhibited an inverse association with CRC patient prognosis. Functionally, the downregulation of LINC00649 exerted anticarcinogenic activities in CRC by decreasing cell proliferation, migration, and invasion and inducing cell apoptosis. Furthermore, the growth of CRC cells in vivo was attenuated after LINC00649 deficiency. Mechanistically, LINC00649 functioned as a competitive endogenous RNA by competitively binding to miR‑432‑5p in CRC cells, inducing an increase in hepatoma‑derived growth factor (HDGF). Ultimately, functional rescue experiments highlighted that the exogenous introduction of miR‑432‑5p inhibitor or HDGF overexpression plasmid partially abated the inhibitory effects of LINC00649 silencing. In conclusion, LINC00649 promoted the aggressiveness of CRC cells by adjusting the miR‑432‑5p/HDGF axis. Thus, the LINC00649/miR‑432‑5p/HDGF pathway may be a promising target for CRC therapy.

View Figures

View References

1	Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018. View Article : Google Scholar : PubMed/NCBI
2	Siegel RL, Miller KD, Goding Sauer A, Fedewa SA, Butterly LF, Anderson JC, Cercek A, Smith RA and Jemal A: Colorectal cancer statistics, 2020. CA Cancer J Clin. 70:145–164. 2020. View Article : Google Scholar : PubMed/NCBI
3	Mitry E, Guiu B, Cosconea S, Jooste V, Faivre J and Bouvier AM: Epidemiology, management and prognosis of colorectal cancer with lung metastases: A 30-year population-based study. Gut. 59:1383–1388. 2010. View Article : Google Scholar : PubMed/NCBI
4	Dekker E and Rex DK: Advances in CRC prevention: Screening and surveillance. Gastroenterology. 154:1970–1984. 2018. View Article : Google Scholar : PubMed/NCBI
5	Tol J, Koopman M, Cats A, Rodenburg CJ, Creemers GJ, Schrama JG, Erdkamp FL, Vos AH, van Groeningen CJ, Sinnige HA, et al: Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N Engl J Med. 360:563–572. 2009. View Article : Google Scholar : PubMed/NCBI
6	Ponting CP, Oliver PL and Reik W: Evolution and functions of long noncoding RNAs. Cell. 136:629–641. 2009. View Article : Google Scholar : PubMed/NCBI
7	Kung JT, Colognori D and Lee JT: Long noncoding RNAs: Past, present, and future. Genetics. 193:651–669. 2013. View Article : Google Scholar : PubMed/NCBI
8	Quinn JJ and Chang HY: Unique features of long non-coding RNA biogenesis and function. Nat Rev Genet. 17:47–62. 2016. View Article : Google Scholar : PubMed/NCBI
9	Schwarzmueller L, Bril O, Vermeulen L and Léveillé N: Emerging role and therapeutic potential of lncRNAs in colorectal cancer. Cancers (Basel). 12:38432020. View Article : Google Scholar : PubMed/NCBI
10	Talebi A, Azizpour M, Agah S, Masoodi M, Mobini GR and Akbari A: The relevance of long noncoding RNAs in colorectal cancer biology and clinical settings. J Cancer Res Ther. 16 (Suppl):S22–S33. 2020. View Article : Google Scholar : PubMed/NCBI
11	Srinivasan S, Selvan ST, Archunan G, Gulyas B and Padmanabhan P: MicroRNAs -the next generation therapeutic targets in human diseases. Theranostics. 3:930–942. 2013. View Article : Google Scholar : PubMed/NCBI
12	Shukla GC, Singh J and Barik S: MicroRNAs: Processing, maturation, target recognition and regulatory functions. Mol Cell Pharmacol. 3:83–92. 2011.PubMed/NCBI
13	Wen XQ, Qian XL, Sun HK, Zheng LL, Zhu WQ, Li TY and Hu JP: MicroRNAs: multifaceted regulators of colorectal cancer metastasis and clinical applications. Onco Targets Ther. 13:10851–10866. 2020. View Article : Google Scholar : PubMed/NCBI
14	Ahadi A: The significance of microRNA deregulation in colorectal cancer development and the clinical uses as a diagnostic and prognostic biomarker and therapeutic agent. Noncoding RNA Res. 5:125–134. 2020. View Article : Google Scholar : PubMed/NCBI
15	Weidle UH, Brinkmann U and Auslaender S: microRNAs and corresponding targets involved in metastasis of colorectal cancer in preclinical in vivo models. Cancer Genomics Proteomics. 17:453–468. 2020. View Article : Google Scholar : PubMed/NCBI
16	Wang L, Cho KB, Li Y, Tao G, Xie Z and Guo B: Long noncoding RNA (lncRNA)-mediated competing endogenous RNA networks provide novel potential biomarkers and therapeutic targets for colorectal cancer. Int J Mol Sci. 20:57582019. View Article : Google Scholar : PubMed/NCBI
17	Guo C, Gao YY, Ju QQ, Zhang CX, Gong M and Li ZL: LINC00649 underexpression is an adverse prognostic marker in acute myeloid leukemia. BMC Cancer. 20:8412020. View Article : Google Scholar : PubMed/NCBI
18	He M, Lin Y and Xu Y: Identification of prognostic biomarkers in colorectal cancer using a long non-coding RNA-mediated competitive endogenous RNA network. Oncol Lett. 17:2687–2694. 2019.PubMed/NCBI
19	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
20	Deng M, Bragelmann J, Schultze JL and Perner S: Web-TCGA: An online platform for integrated analysis of molecular cancer data sets. BMC Bioinformatics. 17:722016. View Article : Google Scholar : PubMed/NCBI
21	Hon KW, Abu N, Ab Mutalib NS and Jamal R: miRNAs and lncRNAs as predictive biomarkers of response to FOLFOX therapy in colorectal cancer. Front Pharmacol. 9:8462018. View Article : Google Scholar : PubMed/NCBI
22	Rivandi M, Pasdar A, Hamzezadeh L, Tajbakhsh A, Seifi S, Moetamani-Ahmadi M, Ferns GA and Avan A: The prognostic and therapeutic values of long noncoding RNA PANDAR in colorectal cancer. J Cell Physiol. 234:1230–1236. 2019. View Article : Google Scholar : PubMed/NCBI
23	Wei L, Wang X, Lv L, Zheng Y, Zhang N and Yang M: The emerging role of noncoding RNAs in colorectal cancer chemoresistance. Cell Oncol (Dordr). 42:757–768. 2019. View Article : Google Scholar : PubMed/NCBI
24	Gao N, Li Y, Li J, Gao Z, Yang Z, Li Y, Liu H and Fan T: Long non-coding RNAs: The regulatory mechanisms, research strategies, and future directions in cancers. Front Oncol. 10:5988172020. View Article : Google Scholar : PubMed/NCBI
25	Samimi H, Sajjadi-Jazi SM, Seifirad S, Atlasi R, Mahmoodzadeh H, Faghihi MA and Haghpanah V: Molecular mechanisms of long non-coding RNAs in anaplastic thyroid cancer: A systematic review. Cancer Cell International. 20:3522020. View Article : Google Scholar : PubMed/NCBI
26	Qi X, Zhang DH, Wu N, Xiao JH, Wang X and Ma W: ceRNA in cancer: Possible functions and clinical implications. J Med Genet. 52:710–718. 2015. View Article : Google Scholar : PubMed/NCBI
27	Ergun S and Oztuzcu S: Oncocers: ceRNA-mediated cross-talk by sponging miRNAs in oncogenic pathways. Tumour Biol. 36:3129–3136. 2015. View Article : Google Scholar : PubMed/NCBI
28	Das S and Bhattacharyya NP: Heat shock factor 1 regulates hsa-miR-432 expression in human cervical cancer cell line. Biochem Biophys Res Commun. 453:461–466. 2014. View Article : Google Scholar : PubMed/NCBI
29	Jiang N, Chen WJ, Zhang JW, Xu C, Zeng XC, Zhang T, Li Y and Wang GY: Downregulation of miR-432 activates Wnt/β-catenin signaling and promotes human hepatocellular carcinoma proliferation. Oncotarget. 6:7866–7879. 2015. View Article : Google Scholar : PubMed/NCBI
30	Chen L, Kong G, Zhang C, Dong H, Yang C, Song G, Guo C, Wang L and Yu H: MicroRNA-432 functions as a tumor suppressor gene through targeting E2F3 and AXL in lung adenocarcinoma. Oncotarget. 7:20041–20053. 2016. View Article : Google Scholar : PubMed/NCBI
31	Luo M, Hu Z, Kong Y and Li L: MicroRNA-432-5p inhibits cell migration and invasion by targeting CXCL5 in colorectal cancer. Exp Ther Med. 21:3012021. View Article : Google Scholar : PubMed/NCBI
32	Lian J, Tang J, Shi H, Li H, Zhen T, Xie W, Zhang F, Yang Y and Han A: Positive feedback loop of hepatoma-derived growth factor and beta-catenin promotes carcinogenesis of colorectal cancer. Oncotarget. 6:29357–29374. 2015. View Article : Google Scholar : PubMed/NCBI
33	Liao F, Liu M, Lv L and Dong W: Hepatoma-derived growth factor promotes the resistance to anti-tumor effects of nordihydroguaiaretic acid in colorectal cancer cells. Eur J Pharmacol. 645:55–62. 2010. View Article : Google Scholar : PubMed/NCBI
34	Hu TH, Lin JW, Chen HH, Liu LF, Chuah SK and Tai MH: The expression and prognostic role of hepatoma-derived growth factor in colorectal stromal tumors. Dis Colon Rectum. 52:319–326. 2009. View Article : Google Scholar : PubMed/NCBI
35	Liao F, Dong W and Fan L: Apoptosis of human colorectal carcinoma cells is induced by blocking hepatoma-derived growth factor. Med Oncol. 27:1219–1226. 2010. View Article : Google Scholar : PubMed/NCBI
36	Hong YG, Huang ZP, Liu QZ, E JF, Gao XH, Xin C, Zhang W, Li P and Hao LQ: MicroRNA-95-3p inhibits cell proliferation and metastasis in colorectal carcinoma by HDGF. Biomed J. 43:163–173. 2020. View Article : Google Scholar : PubMed/NCBI
37	He S, Wang G, Ni J, Zhuang J, Zhuang S, Wang G, Ye Y and Xia W: MicroRNA-511 inhibits cellular proliferation and invasion in colorectal cancer by directly targeting hepatoma-derived growth factor. Oncol Res. 26:1355–1363. 2018. View Article : Google Scholar : PubMed/NCBI
38	Sun B, Gu X, Chen Z and Xiang J: MiR-610 inhibits cell proliferation and invasion in colorectal cancer by repressing hepatoma-derived growth factor. Am J Cancer Res. 5:3635–3644. 2015.PubMed/NCBI