RFC5, regulated by circ_0038985/miR-3614-5p, functions as an oncogene in the progression of colorectal cancer
Huihui Yao
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Search for more papers by this authorXin Zhou
Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Search for more papers by this authorAina Zhou
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Search for more papers by this authorJunjie Chen
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Search for more papers by this authorGuoliang Chen
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Search for more papers by this authorXinyu Shi
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Search for more papers by this authorBo Shi
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Search for more papers by this authorQingliang Tai
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Search for more papers by this authorXiuwei Mi
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Search for more papers by this authorGuoqiang Zhou
Department of Gastrointestinal Surgery, Changshu No. 2 Hospital, Suzhou, Jiangsu, China
Search for more papers by this authorSuo Wang
Department of Gastrointestinal Surgery, Changshu No. 1 Hospital, Suzhou, Jiangsu, China
Search for more papers by this authorJinbing Sun
Department of Gastrointestinal Surgery, Changshu No. 1 Hospital, Suzhou, Jiangsu, China
Search for more papers by this authorXiaodong Yang
Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Search for more papers by this authorYi Yang
Department of Oncological Surgery, Kunshan Traditional Hospital Affiliated to Nanjing University of Chinese Medicine, Kunshan, Jiangsu, China
Search for more papers by this authorHuihua Cao
Department of Oncological Surgery, Kunshan Traditional Hospital Affiliated to Nanjing University of Chinese Medicine, Kunshan, Jiangsu, China
Search for more papers by this authorDiyuan Zhou
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Search for more papers by this authorLiang Sun
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Search for more papers by this authorYizhou Yao
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Search for more papers by this authorCorresponding Author
Songbing He
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Correspondence Songbing He, Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu, China.
Email: [email protected]
Search for more papers by this authorHuihui Yao
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Search for more papers by this authorXin Zhou
Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Search for more papers by this authorAina Zhou
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Search for more papers by this authorJunjie Chen
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Search for more papers by this authorGuoliang Chen
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Search for more papers by this authorXinyu Shi
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Search for more papers by this authorBo Shi
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Search for more papers by this authorQingliang Tai
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Search for more papers by this authorXiuwei Mi
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Search for more papers by this authorGuoqiang Zhou
Department of Gastrointestinal Surgery, Changshu No. 2 Hospital, Suzhou, Jiangsu, China
Search for more papers by this authorSuo Wang
Department of Gastrointestinal Surgery, Changshu No. 1 Hospital, Suzhou, Jiangsu, China
Search for more papers by this authorJinbing Sun
Department of Gastrointestinal Surgery, Changshu No. 1 Hospital, Suzhou, Jiangsu, China
Search for more papers by this authorXiaodong Yang
Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Search for more papers by this authorYi Yang
Department of Oncological Surgery, Kunshan Traditional Hospital Affiliated to Nanjing University of Chinese Medicine, Kunshan, Jiangsu, China
Search for more papers by this authorHuihua Cao
Department of Oncological Surgery, Kunshan Traditional Hospital Affiliated to Nanjing University of Chinese Medicine, Kunshan, Jiangsu, China
Search for more papers by this authorDiyuan Zhou
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Search for more papers by this authorLiang Sun
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Search for more papers by this authorYizhou Yao
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Search for more papers by this authorCorresponding Author
Songbing He
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Correspondence Songbing He, Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu, China.
Email: [email protected]
Search for more papers by this authorHuihui Yao and Xin Zhou contributed equally to this work.
Abstract
Replication factor C 5 (RFC5) is involved in a variety of biological functions of cancer. However, the expression pattern of RFC5 and the underlying mechanisms in colorectal cancer (CRC) remain elusive. Here, we show that RFC5 is significantly upregulated in CRC tissues and cells. Patients with CRC and increased RFC5 levels have an unfavorable prognosis. RFC5 can promote the proliferation, migration, and invasion of CRC cells and inhibit the apoptosis of CRC cells. Additionally, upstream of RFC5, we constructed the competing endogenous RNA network and confirmed that RFC5 in this network was inhibited by miR-3614-5p by directly targeting its 3′-untranslated regions. We verified that circ_0038985, which is positively correlated with RFC5, directly targeted miR-3614-5p. Overexpression of circ_0038985 promoted CRC cell migration and invasion, and these effects were partially reversed by the reintroduction of miR-3614-5p. Moreover, we found that RFC5 may promote the vascular endothelial growth factor A (VEGFa)/vascular endothelial growth factor receptor 2 (VEGFR2)/extracellular signal-regulated protein kinase (ERK) pathway. The knockdown of RFC5 reduced CRC tumorigenesis in vivo. Collectively, these data demonstrate that the circ_0038985/miR-3614-5p/RFC5 axis plays a critical role in the progression of CRC, and RFC5 may promote CRC progression by affecting the VEGFa/VEGFR2/ERK pathway.
CONFLICT OF INTEREST STATEMENT
The authors declare no conflicts of interest.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request. The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.
Supporting Information
Filename | Description |
---|---|
mc23523-sup-0001-Supplementary_materials.7z13.3 MB | Supplementary information. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
REFERENCES
- 1Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021; 71(3): 209-249.
- 2Tian S, Chu Y, Hu J, et al. Tumour-associated neutrophils secrete AGR2 to promote colorectal cancer metastasis via its receptor CD98hc-xCT. Gut. 2022; 71(12): 2489-2501.
- 3Uhlmann F, Cai J, Gibbs E, O'Donnell M, Hurwitz J. Deletion analysis of the large subunit p140 in human replication factor C reveals regions required for complex formation and replication activities. J Biol Chem. 1997; 272: 10058-10064.
- 4Kim J, Robertson K, Mylonas KJL, Gray FC, Charapitsa I, MacNeill SA. Contrasting effects of Elg1-RFC and CTF18-RFC inactivation in the absence of fully functional RFC in fission yeast. Nucleic Acids Res. 2005; 33: 4078-4089.
- 5Branzei D, Foiani M. Maintaining genome stability at the replication fork. Nat Rev Mol Cell Biol. 2010; 11: 208-219.
- 6Broderick S, Rehmet K, Concannon C, Nasheuer HP. Eukaryotic single-stranded DNA binding proteins: central factors in genome stability. Subcell Biochem. 2010; 50: 143-163.
- 7Hu T, Shen H, Li J, Yang P, Gu Q, Fu Z. RFC2, a direct target of miR-744, modulates the cell cycle and promotes the proliferation of CRC cells. J Cell Physiol. 2020; 235(11): 8319-8333.
- 8Zhang Y, Gao X, Yi J, et al. BTF3 confers oncogenic activity in prostate cancer through transcriptional upregulation of replication factor C. Cell Death Dis. 2021; 12(1): 12.
- 9Li Y, Gan S, Ren L, et al. Multifaceted regulation and functions of replication factor C family in human cancers. Am J Cancer Res. 2018; 8(8): 1343-1355.
- 10Wang XC, Yue X, Zhang RX, et al. Genome-wide RNAi screening identifies RFC4 as a factor that mediates radioresistance in colorectal cancer by facilitating nonhomologous end joining repair. Clin Cancer Res. 2019; 25(14): 4567-4579.
- 11Goodall GJ, Wickramasinghe VO. RNA in cancer. Nat Rev Cancer. 2021; 21: 22-36.
- 12Kristensen LS, Jakobsen T, Hager H, Kjems J. The emerging roles of circRNAs in cancer and oncology. Nat Rev Clin Oncol. 2022; 19(3): 188-206.
- 13Sendi H, Yazdimamaghani M, Hu M, et al. Nanoparticle delivery of miR-122 inhibits colorectal cancer liver metastasis. Cancer Res. 2022; 82(1): 105-113.
- 14He J, Chu Z, Lai W, et al. Circular RNA circHERC4 as a novel oncogenic driver to promote tumor metastasis via the miR-556-5p/CTBP2/E-cadherin axis in colorectal cancer. J Hematol Oncol. 2021; 14(1): 194.
- 15Guo Y, Guo Y, Chen C, et al. Circ3823 contributes to growth, metastasis and angiogenesis of colorectal cancer: involvement of miR-30c-5p/TCF7 axis. Mol Cancer. 2021; 20(1): 93.
- 16Mizuno H, Kitada K, Nakai K, Sarai A. PrognoScan: a new database for meta-analysis of the prognostic value of genes. BMC Med Genomics. 2009; 2: 18.
- 17Li JH, Liu S, Zhou H, Qu LH, Yang JH. starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res. 2014; 42(Database issue): D92-D97.
- 18Agarwal V, Bell GW, Nam JW, Bartel DP. Predicting effective microRNA target sites in mammalian mRNAs. eLife. 2015; 4:e05005.
- 19Kim JT, Cho HJ, Park SY, et al. DNA replication and sister chromatid cohesion 1 (DSCC1) of the replication factor complex CTF18-RFC is critical for colon cancer cell growth. J Cancer. 2019; 10(24): 6142-6153.
- 20Siu MKY, Kong DSH, Chan HY, et al. Paradoxical impact of two folate receptors, FRα and RFC, in ovarian cancer: effect on cell proliferation, invasion and clinical outcome. PLoS One. 2012; 7(11):e47201.
- 21Ji Z, Li J, Wang J. Up-regulated RFC2 predicts unfavorable progression in hepatocellular carcinoma. Hereditas. 2021; 158(1): 17.
- 22Liu SM, Chen W, Wang J. Distinguishing between cancer cell differentiation and resistance induced by all-trans retinoic acid using transcriptional profiles and functional pathway analysis. Sci Rep. 2014; 4: 5577.
- 23Ryu DS, Baek GO, Kim EY, Kim KH, Lee DS. Effects of polysaccharides derived from orostachys japonicus on induction of cell cycle arrest and apoptotic cell death in human colon cancer cells. BMB Rep. 2010; 43: 750-755.
- 24Martinez I, Wang J, Hobson KF, Ferris RL, Khan SA. Identification of differentially expressed genes in HPV-positive and HPV-negative oropharyngeal squamous cell carcinomas. Eur J Cancer. 2007; 43: 415-432.
- 25Barfeld SJ, East P, Zuber V, Mills IG. Metaanalysis of prostate cancer gene expression data identifies a novel discriminatory signature enriched for glycosylating enzymes. BMC Med Genomics. 2014; 7: 513.
- 26Varghese S, Xu H, Bartlett D, et al. Isolated hepatic perfusion with high-dose melphalan results in immediate alterations in tumor gene expression in patients with metastatic ocular melanoma. Ann Surg Oncol. 2010; 17: 1870-1877.
- 27Peng W, Han X, Zhang C, et al. FoxM1-mediated RFC5 expression promotes temozolomide resistance. Cell Biol Toxicol. 2017; 33: 527-537.
- 28Caiment F, Gaj S, Claessen S, Kleinjans J. High-throughput data integration of RNA–miRNA–circRNA reveals novel insights into mechanisms of benzo[a] pyrene-induced carcinogenicity. Nucleic Acids Res. 2015; 43: 2525-2534.
- 29Kristensen LS, Andersen MS, Stagsted LVW, Ebbesen KK, Hansen TB, Kjems J. The biogenesis, biology and characterization of circular RNAs. Nat Rev Genet. 2019; 20(11): 675-691.
- 30Cao L, Wang M, Dong Y, et al. Circular RNA circRNF20 promotes breast cancer tumorigenesis and Warburg effect through miR-487a/HIF-1α/HK2. Cell Death Dis. 2020; 11(2): 145.
- 31Huang G, Liang M, Liu H, et al. CircRNA hsa_circRNA_104348 promotes hepatocellular carcinoma progression through modulating miR-187-3p/RTKN2 axis and activating Wnt/β-catenin pathway. Cell Death Dis. 2020; 11(12): 1065.
- 32Ambros V, Bartel B, Bartel DP, et al. A uniform system for microRNA annotation. RNA. 2003; 9(3): 277-279.
- 33Lu TX, Rothenberg ME. MicroRNA. J Allergy Clin Immunol. 2018; 141: 1202-1207.
- 34Han L, Sun Y, Lu C, Ma C, Shi J, Sun D. MiR-3614-5p is a potential novel biomarker for colorectal cancer. Front Genet. 2021; 12:666833.
- 35Li F, Yang H, Kong T, et al. PGAM1, regulated by miR-3614-5p, functions as an oncogene by activating transforming growth factor-β (TGF-β) signaling in the progression of non-small cell lung carcinoma. Cell Death Dis. 2020; 11(8): 710.
- 36Feng Z, Ye Z, Xie J, Chen W, Li W, Xing C. Study on the mechanism of LOXL1-AS1/miR-3614-5p/YY1 signal axis in the malignant phenotype regulation of hepatocellular carcinoma. Biol Direct. 2021; 16(1): 24.
- 37Memczak S, Jens M, Elefsinioti A, et al. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature. 2013; 495(7441): 333-338.
- 38Zheng Q, Bao C, Guo W, et al. Circular RNA profiling reveals an abundant circHIPK3 that regulates cell growth by sponging multiple miRNAs. Nat Commun. 2016; 7:11215.
- 39Piwecka M, Glažar P, Hernandez-Miranda LR, et al. Loss of a mammalian circular RNA locus causes miRNA deregulation and affects brain function. Science. 2017; 357(6357):eaam8526.