Horm Metab Res 2023; 55(10): 701-710
DOI: 10.1055/a-2153-7428
Original Article: Endocrine Research

CircPI4KA Overexpression Enhances Carcinogenesis and Glycolysis Metabolism in Papillary Thyroid Carcinoma by Causing the miR-1287-5p-Mediated NRP2 Expression Elevation

Huanhuan Sun
1   Head, Neck and Thoracic Tumor Surgery, Huangshi Central Hospital, Edong Healthcare, Affiliated Hospital of Hubei Institute of Technology, Huangshi, China
,
Fen Xu
2   Otorhinolaryngology Head and Neck Surgery, Huangshi Central Hospital, Edong Healthcare, Affiliated Hospital of Hubei Institute of Technology, Huangshi, China
,
Dongyang You
1   Head, Neck and Thoracic Tumor Surgery, Huangshi Central Hospital, Edong Healthcare, Affiliated Hospital of Hubei Institute of Technology, Huangshi, China
› Author Affiliations

Abstract

Circular RNAs (circRNAs) are implicated in regulating the pathogenesis of papillary thyroid carcinoma (PTC). Herein, we aimed to investigate how circRNA phosphatidylinositol 4-kinase IIIα (circPI4KA, hsa_circ_0062389) functioned as an oncogene in PTC. CircPI4KA, microRNA-1287-5p (miR-1287-5p) and Neuropilin-2 (NRP2) level detection were completed by reverse transcription-quantitative polymerase chain reaction assay. Cell proliferation was assessed through Cell Counting Kit-8 assay, colony formation assay, and EdU assay. Transwell assay was used for detecting migration and invasion abilities. Cell migration was also determined by wound healing assay. Cell apoptosis was assessed using flow cytometry assay. The protein examination was performed using western blot. Glycolysis was evaluated via commercial kits. Dual-luciferase reporter assay and RNA immunoprecipitation assay were conducted for target analysis. The role of circPI4KA in vivo was explored and analyzed via tumor xenograft assay. CircPI4KA was significantly upregulated in PTC tissues and cells. Knockdown of circPI4KA suppressed proliferation, migration, invasion, glycolysis, and induced apoptosis of PTC cells. CircPI4KA interacted with miR-1287-5p in PTC cells. The antitumor function of circPI4KA downregulation was reversed by inhibition of miR-1287-5p. The miR-1287-5p directly targeted NRP2, and circPI4KA elevated the NRP2 expression by sponging miR-1287-5p. PTC progression was impeded by miR-1287-5p via targeting NRP2. Silencing circPI4KA inhibited tumor growth in vivo through the miR-1287-5p/NRP2 axis. The collective results revealed that circPI4KA induced the upregulation of NRP2 via sponging miR-1287-5p, thus acting as a carcinogenic factor in PTC.

Additional material



Publication History

Received: 16 January 2023

Accepted after revision: 10 August 2023

Article published online:
09 October 2023

© 2023. Thieme. All rights reserved.

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  • References

  • 1 Pitsava G, Stratakis CA, Faucz FR. PRKAR1A and thyroid tumors. Cancers (Basel) 2021; 13: 3834
  • 2 Vasileiadis I, Boutzios G, Karalaki M. et al. Papillary thyroid carcinoma of the isthmus: total thyroidectomy or isthmusectomy?. Am J Surg 2018; 216: 135-139
  • 3 Mansour J, Sagiv D, Alon E. et al. Prognostic value of lymph node ratio in metastatic papillary thyroid carcinoma. J Laryngol Otol 2018; 132: 8-13
  • 4 Verburg FA, Brans B, Mottaghy FM. Molecular nuclear therapies for thyroid carcinoma. Methods 2011; 55: 230-237
  • 5 Zhang Y, Jia DD, Zhang YF. et al. The emerging function and clinical significance of circRNAs in thyroid cancer and autoimmune thyroid diseases. Int J Biol Sci 2021; 17: 1731-1741
  • 6 Hitu L, Gabora K, Bonci EA. et al. MicroRNA in papillary thyroid carcinoma: a systematic review from 2018 to June 2020. Cancers (Basel) 2020; 12: 3118
  • 7 Xu X, Jing J. Advances on circRNAs contribute to carcinogenesis and progression in papillary thyroid carcinoma. Front Endocrinol (Lausanne) 2020; 11: 555243
  • 8 Panda AC. Circular RNAs act as miRNA sponges. Adv Exp Med Biol 2018; 1087: 67-79
  • 9 She Y, Han Y, Zhou G. et al. hsa_circ_0062389 promotes the progression of non-small cell lung cancer by sponging miR-103a-3p to mediate CCNE1 expression. Cancer Genet 2020; 241: 12-19
  • 10 Wang Y, Zong H, Zhou H. Circular RNA circ_0062389 modulates papillary thyroid carcinoma progression via the miR-1179/high mobility group box 1 axis. Bioengineered 2021; 12: 1484-1494
  • 11 Ji F, Du R, Chen T. et al. Circular RNA circSLC26A4 accelerates cervical cancer progression via miR-1287-5p/HOXA7 axis. Mol Ther Nucleic Acids 2020; 19: 413-420
  • 12 Zhang X, Xue C, Cui X. et al. Circ_0075829 facilitates the progression of pancreatic carcinoma by sponging miR-1287-5p and activating LAMTOR3 signalling. J Cell Mol Med 2020; 24: 14596-14607
  • 13 Shao J, Xu Y, Li H. et al. LMCD1 antisense RNA 1 (LMCD1-AS1) potentiates thyroid cancer cell growth and stemness via a positive feedback loop of LMCD1-AS1/miR-1287-5p/GLI2. Ann Transl Med 2020; 8: 1508
  • 14 Fujii T, Shimada K, Asano A. et al. MicroRNA-331-3p suppresses cervical cancer cell proliferation and E6/E7 expression by targeting NRP2. Int J Mol Sci 2016; 17: 8
  • 15 Zhang H, Wang R, Wang M. miR-331-3p suppresses cell invasion and migration in colorectal carcinoma by directly targeting NRP2. Oncol Lett 2019; 18: 6501-6508
  • 16 Lee G, Kang YE, Oh C. et al. Neuropilin-2 promotes growth and progression of papillary thyroid cancer cells. Auris Nasus Larynx 2020; 47: 870-880
  • 17 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
  • 18 Li B, Wang Z, Yang F. et al. miR449a5p suppresses CDK6 expression to inhibit cardiomyocyte proliferation. Mol Med Rep 2021; 23: 14
  • 19 Sun J, Xin K, Leng C. et al. Down-regulation of SNHG16 alleviates the acute lung injury in sepsis rats through miR-128-3p/HMGB3 axis. BMC Pulm Med 2021; 21: 191
  • 20 Eger N, Schoppe L, Schuster S. et al. Circular RNA splicing. Adv Exp Med Biol 2018; 1087: 41-52
  • 21 Huang Y, Zhu Q. Mechanisms regulating abnormal circular RNA biogenesis in cancer. Cancers (Basel) 2021; 13: 4185
  • 22 Wang M, Chen B, Ru Z. et al. CircRNA circ-ITCH suppresses papillary thyroid cancer progression through miR-22-3p/CBL/beta-catenin pathway. Biochem Biophys Res Commun 2018; 504: 283-288
  • 23 Du G, Ma R, Li H. et al. Increased expression of hsa_circ_0002111 and its clinical significance in papillary thyroid cancer. Front Oncol 2021; 11: 644011
  • 24 Li X, Tian Y, Hu Y. et al. CircNUP214 sponges miR-145 to promote the expression of ZEB2 in thyroid cancer cells. Biochem Biophys Res Commun 2018; 507: 168-172
  • 25 Ji X, Sun W, Lv C. et al. Circular RNAs regulate glucose metabolism in cancer cells. Onco Targets Ther 2021; 14: 4005-4021
  • 26 Chen W, Zhang T, Bai Y. et al. Upregulated circRAD18 promotes tumor progression by reprogramming glucose metabolism in papillary thyroid cancer. Gland Surg 2021; 10: 2500-2510
  • 27 Jin Y, Yu LL, Zhang B. et al. Circular RNA hsa_circ_0000523 regulates the proliferation and apoptosis of colorectal cancer cells as miRNA sponge. Braz J Med Biol Res 2018; 51: e7811
  • 28 Cao J, Zhang X, Xu P. et al. Circular RNA circLMO7 acts as a microRNA-30a-3p sponge to promote gastric cancer progression via the WNT2/beta-catenin pathway. J Exp Clin Cancer Res 2021; 40: 6
  • 29 Huang P, Qi B, Yao H. et al. Circular RNA cSMARCA5 regulates the progression of cervical cancer by acting as a microRNA432 sponge. Mol Med Rep 2020; 21: 1217-1223
  • 30 Pan Y, Xu T, Liu Y. et al. Upregulated circular RNA circ_0025033 promotes papillary thyroid cancer cell proliferation and invasion via sponging miR-1231 and miR-1304. Biochem Biophys Res Commun 2019; 510: 334-338
  • 31 Huang Y, Zhang H, Wang L. et al. MiR-613 inhibits the proliferation, migration, and invasion of papillary thyroid carcinoma cells by directly targeting TAGLN2. Cancer Cell Int 2021; 21: 494
  • 32 Li P, Pan X, Zheng Z. et al. Downregulation of miR-519d-3p is associated with poor outcomes and facilitates tumor progression in papillary thyroid cancer by regulating FOXQ1. Horm Metab Res 2021; 53: 625-632