Hsa_circ_0001696 modulates cell proliferation and migration in colorectal cancer

Li,Pei-Fei; Zhang,Zhi-Xin; Yuan,Xin; Song,Hao-Jun; Ding,Xiao-Yun; Xu,Lei

doi:10.3892/ol.2020.12415

Hsa_circ_0001696 modulates cell proliferation and migration in colorectal cancer

Authors:
- Pei-Fei Li
- Zhi-Xin Zhang
- Xin Yuan
- Hao-Jun Song
- Xiao-Yun Ding
- Lei Xu
View Affiliations

Affiliations: Department of Gastroenterology, Ningbo First Hospital, Ningbo, Zhejiang 315010, P.R. China, College of Medicine, Ningbo University, Ningbo, Zhejiang 315211, P.R. China
Published online on: December 31, 2020 https://doi.org/10.3892/ol.2020.12415
Article Number: 154
Copyright: © Li 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

Circular RNAs (circRNAs) are a novel class of endogenous non‑coding RNA molecules that are extensively expressed in a variety of species. Recently, increasing evidence suggests that circRNAs have vital functions indifferent types of human cancer, such as gastric cancer, papillary thyroid cancer and lung cancer. However, the roles of circRNAs in the development of colorectal cancer (CRC) remain unclear. The present study aimed to determine the molecular mechanism underlying hsa_circ_0001696 on the proliferation and migration of CRC cells. Reverse transcription‑quantitative PCR analysis was performed to detect hsa_circ_0001696 expression in 18 paired CRC tissues and matched adjacent normal tissues. RNA interference was also performed to decrease hsa_circ_0001696 expression, and its biological effects were further assessed via flow cytometry, wound healing, colony formation and western blot assays. The results demonstrated that hsa_circ_0001696 expression was significantly lower in CRC tissues compared with adjacent normal tissues. Furthermore, hsa_circ_0001696 knockdown promoted cell proliferation and migration, and the number of cell colonies significantly increased. In addition, western blot analysis demonstrated that the protein expression levels of cyclin‑dependent kinase 4 (CDK4), cyclin D, cyclin E and matrix metalloproteinase 9 (MMP9) increased. Taken together, the results of the present study demonstrated that hsa_circ_0001696 expression was downregulated in CRC tissues, and inhibition of hsa_circ_0001696 promoted cell proliferation and migration by regulating the levels of CDK4, cyclin D, cyclin E and MMP9.

View Figures

View References

1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2018. CA Cancer J Clin. 68:7–30. 2018. View Article : Google Scholar : PubMed/NCBI
2	Chen W, Sun K, Zheng R, Zeng H, Zhang S, Xia C, Yang Z, Li H, Zou X and He J: Cancer incidence and mortality in China, 2014. Chin J Cancer Res. 30:1–12. 2018. View Article : Google Scholar : PubMed/NCBI
3	Bray C, Bell LN, Liang H, Collins D and Yale SH: Colorectal Cancer Screening. WMJ. 116:27–33. 2017.PubMed/NCBI
4	Liang TJ, Wang HX, Zheng YY, Cao YQ, Wu X, Zhou X and Dong SX: APC hypermethylation for early diagnosis of colorectal cancer: A meta-analysis and literature review. Oncotarget. 8:46468–46479. 2017. View Article : Google Scholar : PubMed/NCBI
5	Siegel R, DeSantis C, Virgo K, Stein K, Mariotto A, Smith T, Cooper D, Gansler T, Lerro C, Fedewa S, et al: Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin. 62:220–241. 2012. View Article : Google Scholar : PubMed/NCBI
6	Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK and Kjems J: Natural RNA circles function as efficient microRNA sponges. Nature. 495:384–388. 2013. View Article : Google Scholar : PubMed/NCBI
7	Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J, Rybak A, Maier L, Mackowiak SD, Gregersen LH and Munschauer M: Circular RNAs are a large class of animal RNAs with regulatory potency. Nature. 495:333–338. 2013. View Article : Google Scholar : PubMed/NCBI
8	Ebbesen KK, Kjems J and Hansen TB: Circular RNAs: Identification, biogenesis and function. Biochim Biophys Acta. 1859:163–168. 2016. View Article : Google Scholar : PubMed/NCBI
9	Chen I, Chen CY and Chuang TJ: Biogenesis, identification, and function of exonic circular RNAs. Wiley Interdiscip Rev RNA. 6:563–579. 2015. View Article : Google Scholar : PubMed/NCBI
10	Wilusz JE and Sharp PA: Molecular biology. A circuitous route to noncoding RNA. Science. 340:440–441. 2013. View Article : Google Scholar : PubMed/NCBI
11	Li P, Chen S, Chen H, Mo X, Li T, Shao Y, Xiao B and Guo J: Using circular RNA as a novel type of biomarker in the screening of gastric cancer. Clin Chim Acta. 444:132–136. 2015. View Article : Google Scholar : PubMed/NCBI
12	Wang F, Nazarali AJ and Ji S: Circular RNAs as potential biomarkers for cancer diagnosis and therapy. Am J Cancer Res. 6:1167–1176. 2016.PubMed/NCBI
13	Conn SJ, Pillman KA, Toubia J, Conn VM, Salmanidis M, Phillips CA, Roslan S, Schreiber AW, Gregory PA and Goodall GJ: The RNA binding protein quaking regulates formation of circRNAs. Cell. 160:1125–1134. 2015. View Article : Google Scholar : PubMed/NCBI
14	Zheng Q, Bao C, Guo W, Li S, Chen J, Chen B, Luo Y, Lyu D, Li Y, Shi G, et al: Circular RNA profiling reveals an abundant circHIPK3 that regulates cell growth by sponging multiple miRNAs. Nat Commun. 7:112152016. View Article : Google Scholar : PubMed/NCBI
15	Szabo L and Salzman J: Detecting circular RNAs: Bioinformatic and experimental challenges. Nat Rev Genet. 17:679–692. 2016. View Article : Google Scholar : PubMed/NCBI
16	Chen J, Li Y, Zheng Q, Bao C, He J, Chen B, Lyu D, Zheng B, Xu Y, Long Z, et al: Circular RNA profile identifies circPVT1 as a proliferative factor and prognostic marker in gastric cancer. Cancer Lett. 388:208–219. 2017. View Article : Google Scholar : PubMed/NCBI
17	Weng W, Wei Q, Toden S, Yoshida K, Nagasaka T, Fujiwara T, Cai S, Qin H, Ma Y and Goel A: Circular RNA ciRS-7-A promising prognostic biomarker and a potential therapeutic target in colorectal cancer. Clin Cancer Res. 23:3918–3928. 2017. View Article : Google Scholar : PubMed/NCBI
18	Jeck WR and Sharpless NE: Detecting and characterizing circular RNAs. Nat Biotechnol. 32:453–461. 2014. View Article : Google Scholar : PubMed/NCBI
19	Salzman J, Chen RE, Olsen MN, Wang PL and Brown PO: Cell-type specific features of circular RNA expression. PLoS Genet. 9:e10037772013. View Article : Google Scholar : PubMed/NCBI
20	Akhter R: Circular RNA and Alzheimer's disease. Adv Exp Med Biol. 1087:239–243. 2018. View Article : Google Scholar : PubMed/NCBI
21	Luan W, Shi Y, Zhou Z, Xia Y and Wang J: circRNA_0084043 promote malignant melanoma progression via miR-153-3p/Snail axis. Biochem Biophys Res Commun. 502:22–29. 2018. View Article : Google Scholar : PubMed/NCBI
22	Zhou ZB, Huang GX, Fu Q, Han B, Lu JJ, Chen AM and Zhu L: circRNA.33186 Contributes to the Pathogenesis of Osteoarthritis by Sponging miR-127-5p. Mol Ther. 27:531–541. 2019. View Article : Google Scholar : PubMed/NCBI
23	Li R, Jiang J, Shi H, Qian H, Zhang X and Xu W: CircRNA: A rising star in gastric cancer. Cell Mol Life Sci. 77:1661–1680. 2020. View Article : Google Scholar : PubMed/NCBI
24	Bi W, Huang J, Nie C, Liu B, He G, Han J, Pang R, Ding Z, Xu J and Zhang J: CircRNA circRNA_102171 promotes papillary thyroid cancer progression through modulating CTNNBIP1-dependent activation of β-catenin pathway. J Exp Clin Cancer Res. 37:2752018. View Article : Google Scholar : PubMed/NCBI
25	Zong L, Sun Q, Zhang H, Chen Z, Deng Y, Li D and Zhang L: Increased expression of circRNA_102231 in lung cancer and its clinical significance. Biomed Pharmacother. 102:639–644. 2018. View Article : Google Scholar : PubMed/NCBI
26	Shao Y, Ye M, Jiang X, Sun W, Ding X, Liu Z, Ye G, Zhang X, Xiao B and Guo J: Gastric juice long noncoding RNA used as a tumor marker for screening gastric cancer. Cancer. 120:3320–3328. 2014. View Article : Google Scholar : PubMed/NCBI
27	Shen R, Wang Y, Wang CX, Yin M, Liu HL, Chen JP, Han JQ and Wang WB: MiRNA-155 mediates TAM resistance by modulating SOCS6-STAT3 signalling pathway in breast cancer. Am J Transl Res. 7:2115–2126. 2015.PubMed/NCBI
28	Song H, Sun W, Ye G, Ding X, Liu Z, Zhang S, Xia T, Xiao B, Xi Y and Guo J: Long non-coding RNA expression profile in human gastric cancer and its clinical significances. J Transl Med. 11:2252013. View Article : Google Scholar : PubMed/NCBI
29	Steele SR, Chang GJ, Hendren S, Weiser M, Irani J, Buie WD, Rafferty JF; Clinical Practice Guidelines Committee of the American Society of Colon, ; Rectal Surgeons: Practice Guideline for the surveillance of patients after curative treatment of colon and rectal cancer. Dis Colon Rectum. 58:713–725. 2015. View Article : Google Scholar : PubMed/NCBI
30	Sargent D, Sobrero A, Grothey A, O'Connell MJ, Buyse M, Andre T, Zheng Y, Green E, Labianca R, O'Callaghan C, et al: Evidence for cure by adjuvant therapy in colon cancer: Observations based on individual patient data from 20,898 patients on 18 randomized trials. J Clin Oncol. 27:872–877. 2009. View Article : Google Scholar : PubMed/NCBI
31	Barrett SP and Salzman J: Circular RNAs: Analysis, expression and potential functions. Development. 143:1838–1847. 2016. View Article : Google Scholar : PubMed/NCBI
32	Chen LL and Yang L: Regulation of circRNA biogenesis. RNA Biol. 12:381–388. 2015. View Article : Google Scholar : PubMed/NCBI
33	Guo JU, Agarwal V, Guo H and Bartel DP: Expanded identification and characterization of mammalian circular RNAs. Genome Biol. 15:4092014. View Article : Google Scholar : PubMed/NCBI
34	Jeck WR, Sorrentino JA, Wang K, Slevin MK, Burd CE, Liu J, Marzluff WF and Sharpless NE: Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA. 19:141–157. 2013. View Article : Google Scholar : PubMed/NCBI
35	Bian L, Zhi X, Ma L, Zhang J, Chen P, Sun S, Li J, Sun Y and Qin J: Hsa_circRNA_103809 regulated the cell proliferation and migration in colorectal cancer via miR-532-3p/FOXO4 axis. Biochem Biophys Res Commun. 505:346–352. 2018. View Article : Google Scholar : PubMed/NCBI
36	Han D, Li J, Wang H, Su X, Hou J, Gu Y, Qian C, Lin Y, Liu X, Huang M, et al: Circular RNA circMTO1 acts as the sponge of microRNA-9 to suppress hepatocellular carcinoma progression. Hepatology. 66:1151–1164. 2017. View Article : Google Scholar : PubMed/NCBI
37	Li XN, Wang ZJ, Ye CX, Zhao BC, Li ZL and Yang Y: RNA sequencing reveals the expression profiles of circRNA and indicates that circDDX17 acts as a tumor suppressor in colorectal cancer. J Exp Clin Cancer Res. 37:3252018. View Article : Google Scholar : PubMed/NCBI
38	Zeng K, Chen X, Xu M, Liu X, Hu X, Xu T, Sun H, Pan Y, He B and Wang S: CircHIPK3 promotes colorectal cancer growth and metastasis by sponging miR-7. Cell Death Dis. 9:4172018. View Article : Google Scholar : PubMed/NCBI
39	Yuan Y, Liu W, Zhang Y, Zhang Y and Sun S: CircRNA circ_0026344 as a prognostic biomarker suppresses colorectal cancer progression via microRNA-21 and microRNA-31. Biochem Biophys Res Commun. 503:870–875. 2018. View Article : Google Scholar : PubMed/NCBI
40	Wang R, Zhang S, Chen X, Li N, Li J, Jia R, Pan Y and Liang H: CircNT5E acts as a sponge of miR-422a to promote glioblastoma tumorigenesis. Cancer Res. 78:4812–4825. 2018. View Article : Google Scholar : PubMed/NCBI
41	World Medical Association: World Medical Association Declaration of Helsinki: Ethical principles for medical research involving human subjects. JAMA. 310:2191–2194. 2013. View Article : Google Scholar : PubMed/NCBI