CircRNA_0109291 regulates cell growth and migration in oral squamous cell carcinoma and its clinical significance

Document Type: Original Article


1 Department of Oral Prosthodontics, the Affiliated Stomatological Hospital of Nanchang University, Jiangxi Provincial Key Laboratory of Oral Biomedicine, Nanchang 330006, China

2 Department of Oral and Maxillofacial Surgery, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, China


Objective(s): Circular RNAs (circRNAs), a new class of non-coding RNAs, have emerged as important regulators during tumorigenesis. However, the functions of circRNAs have not been completely clarified in the progression of cancers. In our study, a novel circRNA hsa_circ_0109291 was investigated in oral squamous cell carcinoma (OSCC) tissues and cell lines.
Materials and Methods: The expression profile of circRNAs in OSCC tumor tissues was performed by high-throughput sequencing. The CCK-8 wound healing and apoptosis assay were measured in OSCC cell lines after transfection with si-0109291 or si-NC.
Results: We discovered that hsa_circ_0109291 was significantly increased in OSCC tissues and cell lines compared with their corresponding control group. Knockdown of hsa_circ_0109291 inhibited proliferation and migration of OSCC cell lines in vitro. In addition, inhibition of hsa_circ_0109291 dramatically induced apoptosis of OSCC cells. We further found that high hsa_circ_0109291 levels in OSCC patients resulted in a poorer prognosis than in patients with low hsa_circ_0109291 levels.
Conclusion: These findings indicated that hsa_circ_0109291 correlated with the progression of OSCC and might be a new therapeutic target for the treatment of OSCC.


Main Subjects

1. Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin 2011; 61:212-236.
2. Yang CN, Deng YT, Tang JY, Cheng SJ, Chen ST, Li YJ, et al. MicroRNA-29b regulates migration in oral squamous cell carcinoma and its clinical significance. Oral Oncol 2015; 51:170-177.
3. Kademani D. Oral cancer. Mayo Clin Proc 2007; 82:878-887.
4. Sun CC, Zhang L, Li G, Li SJ, Chen ZL, Fu YF, et al. The lncRNA PDIA3P interacts with miR-185-5p to modulate oral squamous cell carcinoma progression by targeting cyclin D2. Mol Ther Nucleic Acids 2017; 9:100-110.
5. Massano J, Regateiro FS, Januario G, Ferreira A. Oral squamous cell carcinoma: review of prognostic and predictive factors. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006; 102:67-76.
6. Lai YH, Liu H, Chiang WF, Chen TW, Chu LJ, Yu JS, et al. MiR-31-5p-ACOX1 axis enhances tumorigenic fitness in oral squamous cell carcinoma via the promigratory prostaglandin E2. Theranostics 2018; 8:486-504.
7. Hashiguchi Y, Kawano S, Goto Y, Yasuda K, Kaneko N, Sakamoto T, et al. Tumor-suppressive roles of DeltaNp63beta-miR-205 axis in epithelial-mesenchymal transition of oral squamous cell carcinoma via targeting ZEB1 and ZEB2. J Cell Physiol 2017.
8. Ding L, Ren J, Zhang D, Li Y, Huang X, Hu Q, et al. A novel stromal lncRNA signature reprograms fibroblasts to promote the growth of oral squamous cell carcinoma via LncRNA-CAF/interleukin-33. Carcinogenesis 2018.
9. Liang S, Zhang S, Wang P, Yang C, Shang C, Yang J, et al. LncRNA, TUG1 regulates the oral squamous cell carcinoma progression possibly via interacting with Wnt/beta-catenin signaling. Gene 2017; 608:49-57.
10. Chen LL, Yang L. Regulation of circRNA biogenesis. RNA Biol 2015; 12:381-388.
11. Hsu MT, Coca-Prados M. Electron microscopic evidence for the circular form of RNA in the cytoplasm of eukaryotic cells. Nature 1979; 280:339-340.
12. Zhou B, Yu JW. A novel identified circular RNA, circRNA_010567, promotes myocardial fibrosis via suppressing miR-141 by targeting TGF-beta1. Biochem Biophys Res Commun 2017; 487:769-775.
13. Zhao Y, Alexandrov PN, Jaber V, Lukiw WJ. Deficiency in the ubiquitin conjugating enzyme UBE2A in Alzheimer’s disease (AD) is linked to deficits in a natural circular miRNA-7 sponge (circRNA; ciRS-7). Genes (Basel) 2016; 7.
14. Qian Y, Lu Y, Rui C, Qian Y, Cai M, Jia R. Potential significance of circular RNA in human placental tissue for patients with preeclampsia. Cell Physiol Biochem 2016; 39:1380-1390.
15. Liu Q, Zhang X, Hu X, Dai L, Fu X, Zhang J, et al. Circular RNA related to the chondrocyte ECM regulates MMP13 expression by functioning as a MiR-136 ‘Sponge’ in human cartilage degradation. Sci Rep 2016; 6:22572.
16. Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK, et al. Natural RNA circles function as efficient microRNA sponges. Nature 2013; 495:384-388.
17. Meng S, Zhou H, Feng Z, Xu Z, Tang Y, Li P, et al. CircRNA: functions and properties of a novel potential biomarker for cancer. Mol Cancer 2017; 16:94.
18. Zheng Q, Bao C, Guo W, Li S, Chen J, Chen B, et al. Circular RNA profiling reveals an abundant circHIPK3 that regulates cell growth by sponging multiple miRNAs. Nat Commun 2016; 7:11215.
19. Li F, Zhang L, Li W, Deng J, Zheng J, An M, et al. Circular RNA ITCH has inhibitory effect on ESCC by suppressing the Wnt/beta-catenin pathway. Oncotarget 2015; 6:6001-6013.
20. Han D, Li J, Wang H, Su X, Hou J, Gu Y, et al. Circular RNA circMTO1 acts as the sponge of microRNA-9 to suppress hepatocellular carcinoma progression. Hepatology 2017; 66:1151-1164.
21. Liang HF, Zhang XZ, Liu BG, Jia GT, Li WL. Circular RNA circ-ABCB10 promotes breast cancer proliferation and progression through sponging miR-1271. Am J Cancer Res 2017; 7:1566-1576.
22. Zhang J, Liu H, Hou L, Wang G, Zhang R, Huang Y, et al. Circular RNA_LARP4 inhibits cell proliferation and invasion of gastric cancer by sponging miR-424-5p and regulating LATS1 expression. Mol Cancer 2017; 16:151.
23. Zhang XL, Xu LL, Wang F. Hsa_circ_0020397 regulates colorectal cancer cell viability, apoptosis and invasion by promoting the expression of the miR-138 targets TERT and PD-L1. Cell Biol Int 2017; 41:1056-1064.
24. Chen L, Zhang S, Wu J, Cui J, Zhong L, Zeng L, et al. circRNA_100290 plays a role in oral cancer by functioning as a sponge of the miR-29 family. Oncogene 2017; 36:4551-4561.
25. Wang L, Wei Y, Yan Y, Wang H, Yang J, Zheng Z, et al. CircDOCK1 suppresses cell apoptosis via inhibition of miR196a5p by targeting BIRC3 in OSCC. Oncol Rep 2017.
26. Li L, Guo J, Chen Y, Chang C, Xu C. Comprehensive CircRNA expression profile and selection of key CircRNAs during priming phase of rat liver regeneration. BMC Genomics 2017; 18:80.
27. Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J, Rybak A, et al. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature 2013; 495:333-338.
28. Fang S, Guo H, Cheng Y, Zhou Z, Zhang W, Han B, et al. circHECTD1 promotes the silica-induced pulmonary endothelial-mesenchymal transition via HECTD1. Cell Death Dis 2018; 9:396.
29. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 2001; 25:402-408.
30. Momen-Heravi F, Bala S. Emerging role of non-coding RNA in oral cancer. Cell Signal 2018; 42:134-143.
31. Wang L, Wei Y, Yan Y, Wang H, Yang J, Zheng Z, et al. CircDOCK1 suppresses cell apoptosis via inhibition of miR196a5p by targeting BIRC3 in OSCC. Oncol Rep 2018; 39:951-966.
32. Kwon YW, Ahn HS, Park JY, Yang HM, Cho HJ, Kim HS. Imprinted gene Zinc finger protein 127 is a novel regulator of master pluripotency transcription factor, Oct4. BMB Rep 2018; 51:242-248.
33. Jen J, Wang YC. Zinc finger proteins in cancer progression. J Biomed Sci 2016; 23:53.
34. Wang H, Deng X, Zhang J, Ou Z, Mai J, Ding S, et al. Elevated expression of zinc finger protein 703 promotes cell proliferation and metastasis through PI3K/AKT/GSK-3beta signalling in oral squamous cell carcinoma. Cell Physiol Biochem 2017; 44:920-934.
35. Jou YJ, Lin CD, Lai CH, Tang CH, Huang SH, Tsai MH, et al. Salivary zinc finger protein 510 peptide as a novel biomarker for detection of oral squamous cell carcinoma in early stages. Clin Chim Acta 2011; 412:1357-1365.
36. Yang H, Pan L, Xu C, Zhang Y, Li K, Chen S, et al. Overexpression of tumor suppressor gene ZNF750 inhibits oral squamous cell carcinoma metastasis. Oncol Lett 2017; 14:5591-5596.
37. Pang F, Zha R, Zhao Y, Wang Q, Chen D, Zhang Z, et al. MiR-525-3p enhances the migration and invasion of liver cancer cells by downregulating ZNF395. PLoS One 2014; 9:e90867.
38. Chen S, Li T, Zhao Q, Xiao B, Guo J. Using circular RNA hsa_circ_0000190 as a new biomarker in the diagnosis of gastric cancer. Clin Chim Acta 2017; 466:167-171.
39. Yao JT, Zhao SH, Liu QP, Lv MQ, Zhou DX, Liao ZJ, et al. Over-expression of CircRNA_100876 in non-small cell lung cancer and its prognostic value. Pathol Res Pract 2017; 213:453-456.
40. Qin M, Liu G, Huo X, Tao X, Sun X, Ge Z, et al. Hsa_circ_0001649: A circular RNA and potential novel biomarker for hepatocellular carcinoma. Cancer Biomark 2016; 16:161-169.
41. Shang X, Li G, Liu H, Li T, Liu J, Zhao Q, et al. Comprehensive circular RNA profiling reveals that hsa_circ_0005075, a new circular RNA biomarker, is involved in hepatocellular crcinoma development. Medicine (Baltimore) 2016; 95:e3811.
42. Fu L, Yao T, Chen Q, Mo X, Hu Y, Guo J. Screening differential circular RNA expression profiles reveals hsa_circ_0004018 is associated with hepatocellular carcinoma. Oncotarget 2017; 8:58405-58416.