- Open Access
CircCRIM1 promotes nasopharyngeal carcinoma progression via the miR-34c-5p/FOSL1 axis
European Journal of Medical Research volume 27, Article number: 59 (2022)
Nasopharyngeal carcinoma (NPC) is a rare malignancy with multiple risk factors (Epstein–Barr virus, etc.) that seriously threatens the health of people. CircRNAs are known to regulate the tumorigenesis of malignant tumours, including NPC. Moreover, circCRIM1 expression is reported to be upregulated in NPC. Nevertheless, the impact of circCRIM1 on NPC progression is not clear.
An MTT assay was performed to assess cell viability. In addition, cell invasion and migration were assessed by the transwell assay. Dual luciferase assays were performed to assess the association among circCRIM1, miR-34c-5p and FOSL1. Moreover, RT-qPCR was applied to assess mRNA levels, and protein levels were determined by Western blot.
CircCRIM1 and FOSL1 were upregulated in NPC cells, while miR-34c-5p was downregulated. Knockdown of circCRIM1 significantly decreased the invasion, viability and migration of NPC cells. The miR-34c-5p inhibitor notably promoted the malignant behaviour of NPC cells, while miR-34c-5p mimics exerted the opposite effect. Moreover, circCRIM1 could bind with miR-34c-5p, and FOSL1 was identified to be downstream of miR-34c-5p. Furthermore, circCRIM1 downregulation notably inhibited the proliferation and invasion of NPC cells, while this phenomenon was significantly reversed by FOSL1 overexpression.
Silencing circCRIM1 inhibited the tumorigenesis of NPC. Thus, circCRIM1 might be a novel target for NPC.
Nasopharyngeal carcinoma (NPC) is a malignant tumour that forms in the nasopharynx, occurring between the nose and the back of the throat . While the incidence of NPC is high in some countries, especially in North Africa, Southeast Asia and southern China, it is not common among populations . The symptoms of primary NPC include pain, trismus, otitis media and nasal regurgitation, which result from cranial nerve palsy (paralysis) and hearing loss . Currently, surgery and radiotherapy are major strategies for the treatment of NPC, but the efficacies are still not ideal . Moreover, the occurrence of NPC metastasis contributes to organ dysfunction . Thus, new methods for NPC are urgently needed.
CircRNAs play important roles in cell biological processes, such as gene expression, posttranscriptional modification and protein synthesis [6, 7]. Circular RNAs (circRNAs) are a type of closed circular RNA molecule formed by reverse splicing, and their characteristics include high stability, biological evolutionary conservation and tissue expression specificity [8, 9]. Moreover, circRNA dysregulation is known to be closely related to NPC development. For instance, Huang et al. found that circNOTCH1 contributes to NPC progression by mediating the miR-34c-5p/c-Myc axis ; Pan et al. indicated that circLARP4 could alleviate NPC cell growth by repressing ROCK1 . Moreover, circCRIM1 reportedly regulates the tumorigenesis of NPC by regulating FOXQ1 . However, the role of circCRIM1 in NPC remains unclear.
MiRNAs (2–25 nts) are small RNAs that can modulate biological processes by regulating downstream mRNAs [13, 14]. Moreover, circRNAs are involved in NPC development by mediating miRNAs [15, 16]. For instance, the circRNA CDR1 aggravated NPC development by sponging miR-7-5p . Furthermore, silencing circZNF609 suppressed NPC proliferation via the miR-188/ELF2 axis . Moreover, miR-34c-5p inhibited the tumorigenesis of NPC . Nevertheless, the association between circCRIM1 and miR-34c-5p remains largely unknown.
FOS-like antigen 1 (FOSL1) is a member of the AP-1 family, which is closely associated with cellular processes (cell proliferation, etc.) [19, 20]. In addition, FOSL1 is involved in the progression of malignant tumours (oesophageal cancer, lung cancer, etc.) [21, 22]. However, the relationship among circCRIM1, miR-34c-5p and FOSL1 in NPC needs to be explored.
Based on this background, this research focused on the function of circCRIM1 in NPC and the relationship among circCRIM1, miR-34c-5p and FOSL1. We hope that the results of our study will provide a new method for NPC treatment.
Materials and methods
NP69 and human nasopharyngeal carcinoma cells (SUNE-1, CNE2, C666-1, CNE-1, HNE1 and 5-8F) were purchased from the American Type Culture Collection (ATCC) and maintained in DMEM (Thermo Fisher Scientific) containing 10% FBS, penicillin and streptomycin (1%, Thermo Fisher Scientific) at 37 °C and 5% CO2.
The shRNA-directed target CRIM1 (sh-CRIM1) and negative control (sh-NC) were generated by GenePharma (Shanghai, China). Sh-CRIM1 and sh-NC were transfected into NPC cells. After incubation, the supernatant was collected by centrifugation. Then, the supernatants were filtered, and the cells were infected with particles for 48 h. Puromycin (2.5 μg/mL, Sigma, MO, USA) was applied to select the cells.
NPC cells were transfected with the miR-34c-5p mimics/inhibitor, pcDNA3.1-FOSL1 or NC (NC mimics/inhibitor or pcDNA3.1) using Lipofectamine 3000. The miR-34c-5p mimics/inhibitor, pcDNA3.1-FOSL1 and NC were purchased from GenePharma.
NPC cells (5 × 103 cells/well) were treated with the NC or sh-CRIM1 for 12, 24, 48 or 72 h. After that, NPC cells were treated with MTT solution (20 μL) for 2 h. The absorbance (490 nm) was determined by a microplate reader. The protocol was performed as previously described .
Western blot assay
Cells were lysed in RIPA buffer (Beyotime). Equal amounts (20 µg) of protein from each group were separated by SDS–PAGE, and the proteins were then transferred onto a PVDF membrane (Beyotime). Then, the membrane was blocked and incubated with primary antibodies against FOSL1 (1:1000) and GAPDH (1:1000) and the corresponding secondary antibody (1:5000). All antibodies were purchased from Abcam (MA, USA). GAPDH was used for normalization. The protocol was performed as described previously .
Total RNA was obtained with TRIzol (TaKaRa). Subsequently, cDNA was synthesized with a reverse transcription kit (TaKaRa). The protocol was as follows: 94 °C for 2 min, followed by 35 cycles of 94 °C for 30 s and 55 °C for 45 s. The primers were designed by GenePharma, and the data were quantified by the 2−ΔΔCt method. β-actin or U6 was used for normalization. The following primers were designed by GenePharma: circCRIM1, forward, 5ʹ-GCCTTTCCCTGCTACTTGTG-3ʹ and reverse 5ʹ-AGAGCTTCCAAAGGCTAGGG-3ʹ; miR-34c-5p, forward, 5ʹ -GCCGCAGTGCAATGATGAAA-3ʹ and reverse 5ʹ -GTCGTATCCAGTGCAGGGTCCGAGGTATTCGCACTGGATACGACATGCC-3ʹ; FOSL1, forward, 5ʹ-GCCGCAGTGCAATGATGAAA-3ʹ and reverse 5ʹ-GTCGTATCCAGTGCAGGGTCCGAGGTATTCGCACTGGATACGACATGCC-3ʹ; β-actin, forward, 5ʹ-CCAGGTGGTCTCCTCTGA-3ʹ and reverse 5ʹ-GCTGTAGCCAAATCGTTGT-3ʹ; and U6, forward, 5ʹ-CTCGCTTCGGCAGCACA-3ʹ and reverse 5ʹ-AACGCTTCACGAATTTGCGT-3ʹ.
Cell migration and invasion assays
The upper chamber was pretreated with Matrigel (100 μL, not included in the migration assay). NPC cells (1.0 × 106 cells per chamber) in medium (1% FBS) were seeded into the upper chamber. Meanwhile, RPMI 1640 medium containing 10% FBS was added to the lower chamber. Subsequently, the cells in the chamber were rinsed and fixed with 5% glutaraldehyde at 4 °C. Then, the cells were stained with crystal violet (0.1%) for 20 min. The cells were observed under a microscope after the chamber was washed.
Dual luciferase reporter assay
CircCRIM1 and FOSL1 (3ʹ-UTR) sequences with miR-34c-5p binding sites were purchased from GenePharma and cloned into the psiCHECK2 vectors (Promega) to establish circCRIM1 (WT/MUT) and FOSL1 (WT/MUT). NPC cells containing NC/ miR-34c-5p mimics were treated with circCRIM1 (WT/MUT) or FOSL1 (WT/MUT). The data were acquired by the luciferase system (Promega). The protocol was performed as previously described .
Three independent experiments were performed for each group. In addition, all data are expressed as the mean ± standard deviation (SD). Differences were analysed by Student’s t test (only 2 groups) or one-way analysis of variance (ANOVA) followed by Tukey’s test (more than 2 groups). GraphPad Prism (version 7) was used for statistical analysis. P < 0.05 indicated statistically significant differences.
CircCRIM1 and FOSL1 were upregulated in NPC cells, while miR-34c-5p was downregulated
To elucidate the role of circCRIM1, miR-34c-5p and FOSL1 in NPC, RT–qPCR was performed. As revealed in Fig. 1A–C, the expression levels of circCRIM1 and FOSL1 in NPC cells were significantly higher than those in NP69 cells. The miR-34c-5p level in NPC cells was notably lower than that in NP69 cells (Fig. 1A). Since the levels of circCRIM1, miR-34c-5p and FOSL1 were changed most significantly in SUNE-1 and CNE2 cells, these two cell lines were selected for use in subsequent experiments. Taken together, these results demonstrated that circCRIM1 and FOSL1 were upregulated in NPC cells, while miR-34c-5p was downregulated.
Silencing circCRIM1 significantly inhibited the proliferation, migration and invasion of NPC cells
To assess the function of circCRIM1 in NPC, NPC cells were transfected with sh-CRIM1. Then, the efficiency was determined by RT-qPCR. The circCRIM1 levels in NPC cells were significantly decreased by sh-CRIM1, and the expression of miR-34c-5p in NPC cells was notably upregulated by circCRIM1 shRNA (Fig. 2A). In addition, circCRIM1 shRNA attenuated the viability of NPC cells (Fig. 2B). Moreover, silencing circCRIM1 notably suppressed the invasion and migration of NPC cells (Fig. 2C). Altogether, these results demonstrated that silencing circCRIM1 attenuated the migration, proliferation and invasion of NPC cells.
Overexpression of miR-34c-5p alleviated the invasion, proliferation and migration of NPC cells
To assess the effect of miR-34c-5p on NPC cell growth, NPC cells were transfected with miR-34c-5p mimics/inhibitor. As shown in Fig. 3A, the level of miR-34c-5p in NPC cells was notably upregulated by miR-34c-5p but decreased by the miR-34c-5p inhibitor. Moreover, the expression of FOSL1 in cells was markedly upregulated by the miR-34c-5p inhibitor, while miR-34c-5p mimics obviously inhibited FOSL1 levels (Fig. 3B). Additionally, miR-34c-5p upregulation notably inhibited the viability of NPC cells, while miR-34c-5p downregulation exerted the opposite effect (Fig. 3C). Moreover, NPC cell invasion and migration were significantly decreased by miR-34c-5p mimics but increased by miR-34c-5p depletion (Fig. 3D). In summary, overexpression of miR-34c-5p significantly inhibited the invasion, proliferation and migration of NPC cells.
MiR-34c-5p was shown to bind circCRIM1 and FOSL1 in NPC cells
To assess the relationship between miR-34c-5p and circCRIM1 in NPC cells, the dual luciferase assay was performed. As shown in Fig. 4A, circCRIM1 had putative miR-34c-5p binding sites, and the luciferase activity of WT-circCRIM1 was significantly downregulated by miR-34c-5p upregulation. However, miR-34c-5p had a very limited effect on the luciferase activity of MUT-circCRIM1 (Fig. 4A). Moreover, FOSL1 was predicted to be the downstream target of miR-34c-5p, and miR-34c-5p mimics notably inhibited the luciferase activity of WT-FOSL1 (Fig. 4B). Taken together, these results showed that miR-34c-5p could bind with circCRIM1 and FOSL1 in NPC.
FOSL1 upregulation reversed the circCRIM1 shRNA-induced inhibition of NPC cell invasion, proliferation and migration
To elucidate the role of FOSL1 in circCRIM1 shRNA-mediated NPC progression, NPC cells were transfected with pcDNA3.1-FOSL1. As shown in Fig. 5A and B, the FOSL1 levels in NPC cells were decreased by circCRIM1 shRNA, while the effect of sh-CRIM1 on FOSL1 expression was restored by FOSL1 overexpression. In addition, the circCRIM1 shRNA-induced decrease in NPC cell viability was significantly abolished by FOSL1 (Fig. 5C). Consistently, the migration and invasion of circCRIM1 shRNA-treated NPC cells were obviously increased by the upregulation of FOSL1 (Fig. 5D). In summary, overexpression of FOSL1 reversed the circCRIM1 shRNA-induced downregulation of NPC cell invasion, proliferation and migration.
NPC treatments often fail due to NPC metastasis [26, 27]. In this study, circCRIM1 was found to be upregulated in NPC cells, and silencing circCRIM1 attenuated the invasion, proliferation and migration of NPC cells. CircCRIM1 knockdown can reportedly alleviate the tumorigenesis of NPC . In addition, our research suggested that circCRIM1 binds with miR-34c-5p in NPC cells, and FOSL1 was identified to be downstream of miR-34c-5p in NPC cells. Therefore, our study first explored the relationship among circCRIM1, miR-34c-5p and FOSL1 in NPC cells.
It has been reported that circRNAs can regulate cellular processes, enabling them to thereby regulate the progression of multiple diseases, including cancers [28, 29]. Previous studies have indicated that circCRIM1 plays a role in malignant tumours. For example, silencing circCRIM1 disrupted osteosarcoma cell invasion, proliferation and migration via mediation of the miR-432-5p/HDAC4 axis . Our research suggested an association between circCRIM1 and the miR-34c-5p/FOSL1 axis, which further supports its role in NPC. MiR-34c-5p is a key inhibitor of cancer progression [31, 32]. Previous studies suggested that silencing circCRIM1 attenuates the progression of NPC via its binding to miR-34c-5p. Moreover, Hong et al. suggested that FOXQ1 is upregulated by circCRIM1 in NPC , in contrast to our finding. FOXQ1 was reported to promote cell growth . Thus, the similar functions of FOSL1 and FOXQ1 might account for the various functions of circCRIM1 in NPC. The above results suggest that circCRIM1 promotes NPC.
A previous study demonstrated that c-Myc and Notch1 are potentially direct targets of miR-34c-5p [10, 18]. FOSL1 reportedly participates in cancer tumorigenesis. For instance, FOSL1 upregulation led to the tumorigenesis of head and neck squamous cell carcinoma , and FOSL1 promoted the proliferation of colorectal cancer cells . Consistently, the results of our study further suggest that FOSL1 is the target of miR-34c-5p in NPC cells, which furthers our understanding of the mechanism underlying miR-34c-5p in NPC. Moreover, a previous study indicated that EGFR-PKM2 signalling promotes the malignant behaviour of NPC cells via the inactivation of FOSL1 and ANTXR2 , consistent with our results herein. EGFR is known to be the key promoter of multiple cancers (e.g. NSCLC, breast cancer [37,38,39]), and FOSL1 has been confirmed to be indirectly targeted by circCRIM1. Thus, circCRIM1 might act as the promoter of the EGFR pathway, and we plan to investigate the relationship between circCRIM1 and the EGFR pathway in the future.
Indeed, this study does have the following limitations: (1) more miRNAs downstream of circCRIM1 in NPC need to be explored, and (2) additional targets of miR-34c-5p in NPC remain unexplored. Thereafter, more analysis is necessary in the future.
This research was limited by the lack of in vivo experiments, which are needed to further validate the results. Thus, more investigations are needed in the future.
In conclusion, silencing circCRIM1 significantly attenuated the development of NPC through the miR-34c-5p/FOSL1 axis. Therefore, our study might shed new light on exploring new strategies for NPC treatment.
Availability of data and materials
circRNA cysteine-rich transmembrane bone morphogenetic protein regulator 1
Transcription factor activator protein-1
Zou R, Yuan JJ, Li Q, Ding JW, Liao B, Tu ZW, et al. The clinical outcomes and toxicities of induction chemotherapy followed by concurrent chemoradiotherapy plus adjuvant chemotherapy in locoregionally advanced nasopharyngeal carcinoma. Front Oncol. 2020;10:619625.
Miao X, Deng Z, Wang S, Weng H, Zhang X, Li H, et al. IAP-1 promoted cisplatin resistance in nasopharyngeal carcinoma via inhibition of caspase-3-mediated apoptosis. Am J Cancer Res. 2021;11(3):640–67.
Parlak S, Yazici G, Dolgun A, Ozgen B. The evolution of bone marrow signal changes at the skull base in nasopharyngeal carcinoma patients treated with radiation therapy. Radiol Med. 2021;126(6):818–26.
Zheng W, Ye W, Wu Z, Huang X, Xu Y, Chen Q, et al. Identification of potential plasma biomarkers in early-stage nasopharyngeal carcinoma-derived exosomes based on RNA sequencing. Cancer Cell Int. 2021;21(1):185.
Liu C, Guo P, Zhou L, Wang Y, Tian S, Ding Y, et al. A practical method to screen and identify functioning biomarkers in nasopharyngeal carcinoma. Sci Rep. 2021;11(1):7294.
Nan A, Chen L, Zhang N, Jia Y, Li X, Zhou H, et al. Circular RNA circNOL10 inhibits lung cancer development by promoting SCLM1-mediated transcriptional regulation of the humanin polypeptide family. Adv Sci. 2019;6(2):1800654.
Qin C, Liu CB, Yang DG, Gao F, Zhang X, Zhang C, et al. Circular RNA expression alteration and bioinformatics analysis in rats after traumatic spinal cord injury. Front Mol Neurosci. 2018;11:497.
Fu B, Zhang A, Li M, Pan L, Tang W, An M, et al. Circular RNA profile of breast cancer brain metastasis: identification of potential biomarkers and therapeutic targets. Epigenomics. 2018;10(12):1619–30.
Zheng S, Gu T, Bao X, Sun J, Zhao J, Zhang T, et al. Circular RNA hsa_circ_0014243 may serve as a diagnostic biomarker for essential hypertension. Exp Ther Med. 2019;17(3):1728–36.
Huang W, Song W, Jiang Y, Chen L, Lu H. c-Myc-induced circ-NOTCH1 promotes aggressive phenotypes of nasopharyngeal carcinoma cells by regulating the miR-34c-5p/c-Myc axis. Cell Biol Int. 2021;45(7):1436–47.
Pan JY, Bao XL, Zhu K. Circular RNA_LARP4 inhibits cell proliferation and invasion of nasopharyngeal carcinoma by repressing ROCK1. Eur Rev Med Pharmacol Sci. 2020;24(24):12624.
Hong X, Liu N, Liang Y, He Q, Yang X, Lei Y, et al. Circular RNA CRIM1 functions as a ceRNA to promote nasopharyngeal carcinoma metastasis and docetaxel chemoresistance through upregulating FOXQ1. Mol Cancer. 2020;19(1):33.
Shin JH, Shin DH, Kim JS. Let-7 miRNA and CDK4 siRNA co-encapsulated in Herceptin-conjugated liposome for breast cancer stem cells. Asian J Pharm Sci. 2020;15(4):472–81.
Guo X, Luo Z, Xia T, Wu L, Shi Y, Li Y. Identification of miRNA signature associated with BMP2 and chemosensitivity of TMZ in glioblastoma stem-like cells. Genes Dis. 2020;7(3):424–39.
Zhong Q, Huang J, Wei J, Wu R. Circular RNA CDR1as sponges miR-7-5p to enhance E2F3 stability and promote the growth of nasopharyngeal carcinoma. Cancer Cell Int. 2019;19:252.
Zhang Y, Liu Q, Liao Q. CircHIPK3: a promising cancer-related circular RNA. Am J Transl Res. 2020;12(10):6694–704.
Li M, Li Y, Yu M. CircRNA ZNF609 knockdown suppresses cell growth via modulating miR-188/ELF2 axis in nasopharyngeal carcinoma. Onco Targets Ther. 2020;13:2399–409.
Xu X, Yan H, Zhang L, Liu J, Huang Y, Cheng H. Up-regulation of miR-34c-5p inhibits nasopharyngeal carcinoma cells by mediating NOTCH1. Biosci Rep. 2020.
Nitkin CR, Xia S, Menden H, Yu W, Xiong M, Heruth DP, et al. FOSL1 is a novel mediator of endotoxin/lipopolysaccharide-induced pulmonary angiogenic signaling. Sci Rep. 2020;10(1):13143.
Evellin S, Galvagni F, Zippo A, Neri F, Orlandini M, Incarnato D, et al. FOSL1 controls the assembly of endothelial cells into capillary tubes by direct repression of alphav and beta3 integrin transcription. Mol Cell Biol. 2013;33(6):1198–209.
Shen S, Li K, Liu Y, Liu X, Liu B, Ba Y, et al. Silencing lncRNA AGAP2-AS1 upregulates miR-195-5p to repress migration and invasion of EC cells via the decrease of FOSL1 expression. Mol Ther Nucleic Acids. 2020;20:331–44.
Elangovan IM, Vaz M, Tamatam CR, Potteti HR, Reddy NM, Reddy SP. FOSL1 promotes Kras-induced lung cancer through amphiregulin and cell survival gene regulation. Am J Respir Cell Mol Biol. 2018;58(5):625–35.
Vuletic A, Konjevic G, Milanovic D, Ruzdijic S, Jurisic V. Antiproliferative effect of 13-cis-retinoic acid is associated with granulocyte differentiation and decrease in cyclin B1 and Bcl-2 protein levels in G0/G1 arrested HL-60 cells. Pathol Oncol Res. 2010;16(3):393–401.
Radenkovic S, Konjevic G, Nikitovic M, Stojanovic Rundic S, Plesinac Karapandzic V, Milovic Kovacevic M, et al. Evaluation of Cyclin D1 expression by western blotting methods and immunohistochemistry in breast cancer patients. J BUON. 2021;26(2):475–82.
Ferri C, Di Biase A, Bocchetti M, Zappavigna S, Wagner S, Le Vu P, et al. MiR-423-5p prevents MALAT1-mediated proliferation and metastasis in prostate cancer. J Exp Clin Cancer Res. 2022;41(1):20.
Li G, Qiu Y, Su Z, Ren S, Liu C, Tian Y, et al. Genome-wide analyses of radioresistance-associated miRNA expression profile in nasopharyngeal carcinoma using next generation deep sequencing. PLoS ONE. 2013;8(12):e84486.
Luo Z, Zhang L, Li Z, Li X, Li G, Yu H, et al. An in silico analysis of dynamic changes in microRNA expression profiles in stepwise development of nasopharyngeal carcinoma. BMC Med Genomics. 2012;5:3.
Liu D, Liu W, Chen X, Yin J, Ma L, Liu M, et al. circKCNN2 suppresses the recurrence of hepatocellular carcinoma at least partially via regulating miR-520c-3p/methyl-DNA-binding domain protein 2 axis. Clin Transl Med. 2022;12(1):e662.
Zhang Q, Wang Z, Cai H, Guo D, Xu W, Bu S, et al. CircPLK1 acts as a carcinogenic driver to promote the development of malignant pleural mesothelioma by governing the miR-1294/HMGA1 pathway. Biochem Genet. 2022.
Liu J, Feng G, Li Z, Li R, Xia P. Knockdown of CircCRIM1 inhibits HDAC4 to impede osteosarcoma proliferation, migration, and invasion and facilitate autophagy by targeting miR-432-5p. Cancer Manag Res. 2020;12:10199–210.
Kahl I, Mense J, Finke C, Boller AL, Lorber C, Gyorffy B, et al. The cell cycle-related genes RHAMM, AURKA, TPX2, PLK1, and PLK4 are associated with the poor prognosis of breast cancer patients. J Cell Biochem. 2022.
Shen Z, Sun S. CircPTCH1 promotes migration in lung cancer by regulating MYCN expression through miR-34c-5p. Onco Targets Ther. 2021;14:4779–89.
Wang X, Zhu X. Tumor forkhead box Q1 is elevated, correlates with increased tumor size, international federation of gynecology and obstetrics stage but worse overall survival in epithelial ovarian cancer patients. Cancer Biother Radiopharm. 2021.
Wan Y, Hoyle RG, Xie N, Wang W, Cai H, Zhang M, et al. A super-enhancer driven by FOSL1 controls miR-21-5p expression in head and neck squamous cell carcinoma. Front Oncol. 2021;11:656628.
Yukimoto R, Nishida N, Hata T, Fujino S, Ogino T, Miyoshi N, et al. Specific activation of glycolytic enzyme enolase 2 in BRAF V600E-mutated colorectal cancer. Cancer Sci. 2021;112(7):2884–94.
Chen S, Youhong T, Tan Y, He Y, Ban Y, Cai J, et al. EGFR-PKM2 signaling promotes the metastatic potential of nasopharyngeal carcinoma through induction of FOSL1 and ANTXR2. Carcinogenesis. 2020;41(6):723–33.
Shiri I, Amini M, Nazari M, Hajianfar G, Haddadi Avval A, Abdollahi H, et al. Impact of feature harmonization on radiogenomics analysis: Prediction of EGFR and KRAS mutations from non-small cell lung cancer PET/CT images. Comput Biol Med. 2022;142:105230.
Feng J, Li S, Zhang B, Duan N, Zhou R, Yan S, et al. FGFC1 exhibits anti-cancer activity via inhibiting NF-kappaB signaling pathway in EGFR-Mutant NSCLC cells. Mar Drugs. 2022;20(1):76.
Lieser RM, Li Q, Chen W, Sullivan MO. Incorporation of endosomolytic peptides with varying disruption mechanisms into EGFR-Targeted protein conjugates: the effect on intracellular protein delivery and EGFR specificity in breast cancer cells. Mol Pharm. 2022;19(2):661–73.
This work was supported by grants from Changsha Science and Technology Bureau (kq2004104) and Natural Science Foundation of Hunan Province (2019JJ40159).
Ethics approval and consent to participate
This article does not contain any studies with human participants or animals performed by any of the authors.
Consent for publication
The author declared no competing interests in this study.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
About this article
Cite this article
He, W., Zhou, X., Mao, Y. et al. CircCRIM1 promotes nasopharyngeal carcinoma progression via the miR-34c-5p/FOSL1 axis. Eur J Med Res 27, 59 (2022). https://doi.org/10.1186/s40001-022-00667-2