Down-regulation of circPVRL3 promotes the proliferation and migration of gastric cancer cells

Scientific Reports - Tập 8 Số 1
Handong Sun1, Zhipeng Xu2, Zhiqiang Sun3, Bin Zhu1, Qian Wang1, Jian Zhou1, Hui Jin4, Andi Zhao5, Weiwei Tang5, Xiufeng Cao1
1Department of Oncology Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
2Department of Oncology Surgery, Nanjing SIR RUN RUN Hospital, Nanjing Medical University, Nanjing, China
3Nanjing Medical University, School of Pharmacy, Nanjing, China
4Department of Hematology, the First Affiliated Hospital, Nanjing Medical University, Nanjing, China
5Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, China

Tóm tắt

AbstractCircular RNA (circRNA) is a key regulator in the development and progression of various types of carcinomas. However, its role in gastric cancer (GC) tumorigenesis is not well understood. The present study aimed to investigate the expression profile and potential modulation of circRNAs on GC carcinogenesis. Human circRNA microarray was performed to screen for abnormally expressed circRNA in GC tissue. Results showed that a decrease in the circPVRL3 expression level was associated with the presence of GC, and also with higher TNM stage and lower overall survival rates compared with that in adjacent noncancerous tissues. In vitro assays of the GC cell lines MKN-45 and MGC-803 demonstrated that knockdown of circPVRL3 promoted cell proliferation significantly. Prediction and annotation revealed circPVRL3 was able to sponge to 9 miRNAs and may be also able to have a binding with AGO2, FUS, LIN28A, PTB, and EIF4A3. In addition, based on the structure of internal ribosomal entry sites, open reading frame, and m6A modification, circPVRL3 may have the potential ability to encode proteins. Taken together, our study indicated that down-regulation of circPVRL3 could promote the proliferation in gastric carcinoma and have potential to encode protein.

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Tài liệu tham khảo

Nagini, S. Carcinoma of the stomach: A review of epidemiology, pathogenesis, molecular genetics and chemoprevention. World J Gastrointest Oncol. 4, 156–169 (2012).

Chen, W. et al. Cancer statistics in China, 2015. CA Cancer J Clin. 66, 115–132 (2016).

Yagi, K. et al. Diagnosis of Early Gastric Cancer by Magnifying Endoscopy with NBI from Viewpoint of Histological Imaging: Mucosal Patterning in terms of White Zone Visibility and Its Relationship to Histology. Diagn Ther Endosc. 2012, 954809 (2012).

Narikazu, B. Past and Present Achievements, and Future Direction of the Gastrointestinal Oncology Study Group (GIOSG), a Division of Japan Clinical Oncology Group (JCOG). Jpn J Clin Oncol. 41, 1315–1321 (2011).

Terracciano, D. et al. The role of a new class of long noncoding RNAs transcribed from ultraconserved regions in cancer. Biochim Biophys Acta. 1868, 449–455 (2017).

Suzuki, H. & Tsukahara, T. A view of pre-mRNA splicing from RNase R resistant RNAs. Int. J. Mol. Sci. 15, 9331–9342 (2014).

Memczak, S. et al. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature. 495, 333–338 (2013).

Salzman, J. et al. Cell-type specific features of circular RNA expression. PLoS Genet. 9, e1003777 (2013).

Li, Z. et al. Exon-intron circular RNAs regulate transcription in the nucleus. Nat. Struct. Mol. Biol. 22, 256–264 (2015).

Hentze, M. W. & Preiss, T. Circular RNAs: splicing’s enigma variations. EMBO J. 32, 923–925 (2013).

Wang, Y. & Wang, Z. Efficient backsplicing produces translatable circular mRNAs. RNA. 21, 172–179 (2015).

Li, Y. et al. Circular RNA is enriched and stable in exosomes: a promising biomarker for cancer diagnosis. Cell Res. 25, 981–984 (2015).

Barrett, S. P. & Salzman, J. Circular RNAs: analysis, expression and potential functions. Development. 143, 1838–1847 (2016).

Wang, K. et al. Androgen receptor (AR) promotes clear cell renal cell carcinoma (ccRCC) migration and invasion via altering the circHIAT1/miR-195-5p/29a-3p/29c-3p/CDC42 signals. Cancer Lett. 394, 1–12 (2017).

Chen, J. et al. Circular RNA profile identifies circPVT1 as a proliferative factor and prognostic marker in gastric cancer. Cancer lett. 388, 208–219 (2017).

Li, T. et al. Plasma circular RNA profiling of patients with gastric cancer and their droplet digital RT-PCR detection. J Mol Med. 96, 85–96 (2018).

Li, P. et al. Using circular RNA as a novel type of biomarker in the screening of gastric cancer. Clin Chim Acta. 444, 132–136 (2015).

Feng, Y. et al. Naturally existing isoforms of miR-222 have distinct functions Naturally existing isoforms of miR-222 have distinct functions. Nucleic Acids Research. 45, 11371–11385 (2017).

Neumann, D. P., Goodall, G. J. & Gregory, P. A. Regulation of splicing and circularisation of RNA in epithelial mesenchymal plasticity. Semin Cell Dev Biol. 75, 50–60 (2017).

Zhou, L. et al. Silencing of thrombospondin-1 is critical for myc-induced metastatic phenotypes in medulloblastoma. Cancer Res. 70, 8199–8210 (2010).

Rusinek, D. et al. BRAFV600E-associated gene expression profile: Early changes in the transcriptome, based on a transgenic mouse model of papillary thyroid carcinoma. PLoS One. 10, e0143688 (2015).

Gao, D. et al. Screening circular RNA related to chemotherapeutic resistance in breast cancer. Epigenomics. 9, 1175–1188 (2017).

Zhong, Z., Lv, M. & Chen, J. Screening differential circular RNA expression profiles reveals the regulatory role of circTCF25-miR-103a-3p/miR-107-CDK6 pathway in bladder carcinoma. Sci Rep. 6, 30919 (2016).

Zheng, Y. et al. The expression level of miR-203 in patients with gastric cancer and its clinical significance. Pathol Res Pract. 213, 1515–1518 (2017).

Gao, P. et al. microRNA-203 suppresses invasion of gastric cancer cells by targeting ERK1/2/Slug/E-cadherin signaling. Cancer Biomark. 19, 11–2 (2017).

Zhang, J. et al. MicroRNA-638 inhibits cell proliferation by targeting phospholipase D1 in human gastric carcinoma. Protein Cell. 6, 680–688 (2015).

Wei, J. et al. MicroRNA-31 Function as a Suppressor Was Regulated by Epigenetic Mechanisms in Gastric Cancer. Biomed Res Int. 2017, 5348490 (2017).

Zhang, X. et al. Upregulation of microRNA-31 targeting integrin α5 suppresses tumor cell invasion and metastasis by indirectly regulating PI3K/AKT pathway in human gastric cancer SGC7901 cells. Tumour Biol. 37, 8317–8325 (2017).

Hansen, T. B. et al. Natural RNA circles function as efficient microRNA sponges. Nature. 495, 384–388 (2013).

Zhang, Y. et al. Circular intronic long noncoding RNAs. Mol Cell. 51, 792–806 (2013).

Ashwal-Fluss, R. et al. circRNA biogenesis competes with pre-mRNA splicing. Mol Cell. 56, 55–66 (2014).

Pamudurti, N. R. et al. Translation of circRNAs. Mol Cell. 66, 9–21e7 (2017).

Zhou, C. et al. Genome-Wide Maps of m6A circRNAs Identify Widespread and Cell-Type-Specific Methylation Patterns that Are Distinct from mRNAs. Cell reports. 20, 2262–227 (2017).

Yang, Y. et al. Extensive translation of circular RNAs driven by N6-methyladenosine. Cell Res. 27, 626–641 (2017).

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Tập 8 Số 1

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