RPF2 mediates the CARM1‑MYCN axis to promote chemotherapy resistance in colorectal cancer cells

Lu,Macheng; Hu,Xingqian; Cheng,Cong; Zhang,Yuan; Huang,Longchang; Kong,Xiangpeng; Li,Zengyao; Zhang,Qiuhua; Zhang,Ye

doi:10.3892/or.2023.8670

RPF2 mediates the CARM1‑MYCN axis to promote chemotherapy resistance in colorectal cancer cells

Authors:
- Macheng Lu
- Xingqian Hu
- Cong Cheng
- Yuan Zhang
- Longchang Huang
- Xiangpeng Kong
- Zengyao Li
- Qiuhua Zhang
- Ye Zhang
View Affiliations

Affiliations: Department of General Surgery, Nanjing Medical University Affiliated Wuxi People's Hospital, Wuxi, Jiangsu 214023, P.R. China, Department of General Surgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Xuanwu, Nanjing, Jiangsu 210093, P.R. China, Department of Nephrology, The Wuxi No. 2 People's Hospital, Wuxi, Jiangsu 214023, P.R. China
Published online on: November 21, 2023 https://doi.org/10.3892/or.2023.8670
Article Number: 11
Copyright: © Lu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Ribosome production factor 2 homolog (RPF2) plays an important role in the life processes of ribosomal biogenesis; however, the function and mechanism of RPF2 in tumors are unclear. The present study demonstrated that RPF2 expression is involved in chemoresistance in colorectal cancer (CRC) cells. The current study demonstrated that upregulation of RPF2 expression in CRC promoted resistance to chemotherapeutic agents in CRC cells, whereas knockdown of RPF2 leads to increased sensitivity of CRC to chemotherapy. In addition, it was found that overexpression of RPF2 led to an increase in ATP‑binding cassette (ABC)B1 expression in CRC cells; accordingly, inhibition of RPF2 reduced the level of ABCB1 in CRC cells, thus suggesting that ABCB1 may be a downstream factor of RPF2 in the promotion of chemotherapy resistance to CRC. The results also suggested that the expression of N‑myc proto‑oncogene protein (MYCN), an upstream regulator of ABCB1, was affected by RPF2 in CRC cells. In addition, it was also found that the downstream protein coactivator‑associated arginine methyltransferase 1 (CARM1) of RPF2 existed in direct binding to MYCN and this interaction was regulated by RPF2. The above results suggested that RPF2 is probably regulated ABCB1 expression in CRC through the CARM1‑MYCN pathway, thereby promoting CRC drug resistance.

View Figures

View References

1	Siegel RL, Miller KD, Fuchs HE and Jemal A: Cancer statistics, 2022. CA Cancer J Clin. 72:7–33. 2022. View Article : Google Scholar : PubMed/NCBI
2	Dekker E, Tanis PJ, Vleugels JLA, Kasi PM and Wallace MB: Colorectal cancer. Lancet. 394:1467–1480. 2019. View Article : Google Scholar : PubMed/NCBI
3	Micic J, Li Y, Wu S, Wilson D, Tutuncuoglu B, Gao N and Woolford JL Jr: Coupling of 5S RNP rotation with maturation of functional centers during large ribosomal subunit assembly. Nat Commun. 11:37512020. View Article : Google Scholar : PubMed/NCBI
4	Castillo Duque de Estrada NM, Thoms M, Flemming D, Hammaren HM, Buschauer R, Ameismeier M, Baßler J, Beck M, Beckmann R and Hurt E: Structure of nascent 5S RNPs at the crossroad between ribosome assembly and MDM2-p53 pathways. Nat Struct Mol Biol. 30:1119–1131. 2023. View Article : Google Scholar : PubMed/NCBI
5	Li H, Hu X, Cheng C, Lu M, Huang L, Dou H, Zhang Y and Wang T: Ribosome production factor 2 homolog promotes migration and invasion of colorectal cancer cells by inducing epithelial-mesenchymal transition via AKT/Gsk-3β signaling pathway. Biochem Biophys Res Commun. 597:52–57. 2022. View Article : Google Scholar : PubMed/NCBI
6	Qu S, Huang X, Guo X, Zheng Z, Wei T and Chen B: Metastasis related epithelial-mesenchymal transition signature predicts prognosis and response to chemotherapy in acute myeloid leukemia. Drug Des Devel Ther. 17:1651–1663. 2023. View Article : Google Scholar : PubMed/NCBI
7	Gelatti ACZ, Drilon A and Santini FC: Optimizing the sequencing of tyrosine kinase inhibitors (TKIs) in epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). Lung Cancer. 137:113–122. 2019. View Article : Google Scholar : PubMed/NCBI
8	Huang J, Li H and Ren G: Epithelial-mesenchymal transition and drug resistance in breast cancer (review). Int J Oncol. 47:840–848. 2015. View Article : Google Scholar : PubMed/NCBI
9	Uramoto H, Shimokawa H, Hanagiri T, Kuwano M and Ono M: Expression of selected gene for acquired drug resistance to EGFR-TKI in lung adenocarcinoma. Lung Cancer. 73:361–365. 2011. View Article : Google Scholar : PubMed/NCBI
10	Arumugam T, Ramachandran V, Fournier KF, Wang H, Marquis L, Abbruzzese JL, Gallick GE, Logsdon CD, McConkey DJ and Choi W: Epithelial to mesenchymal transition contributes to drug resistance in pancreatic cancer. Cancer Res. 69:5820–5828. 2009. View Article : Google Scholar : PubMed/NCBI
11	McConkey DJ, Choi W, Marquis L, Martin F, Williams MB, Shah J, Svatek R, Das A, Adam L, Kamat A, et al: Role of epithelial-to-mesenchymal transition (EMT) in drug sensitivity and metastasis in bladder cancer. Cancer Metastasis Rev. 28:335–344. 2009. View Article : Google Scholar : PubMed/NCBI
12	Li S, Zhang W, Yin X, Xing S, Xie HQ, Cao Z and Zhao B: Mouse ATP-binding cassette (ABC) transporters conferring multi-drug resistance. Anticancer Agents Med Chem. 15:423–432. 2015. View Article : Google Scholar : PubMed/NCBI
13	Zhu Y, Huang S, Chen S, Chen J, Wang Z, Wang Y and Zheng H: SOX2 promotes chemoresistance, cancer stem cells properties, and epithelial-mesenchymal transition by β-catenin and Beclin1/autophagy signaling in colorectal cancer. Cell Death Dis. 12:4492021. View Article : Google Scholar : PubMed/NCBI
14	Wang YJ, Zhang YK, Zhang GN, Al Rihani SB, Wei MN, Gupta P, Zhang XY, Shukla S, Ambudkar SV, Kaddoumi A, et al: Regorafenib overcomes chemotherapeutic multidrug resistance mediated by ABCB1 transporter in colorectal cancer: In vitro and in vivo study. Cancer Lett. 396:145–154. 2017. View Article : Google Scholar : PubMed/NCBI
15	Ghosh S: Cisplatin: The first metal based anticancer drug. Bioorg Chem. 88:1029252019. View Article : Google Scholar : PubMed/NCBI
16	van Driel WJ, Koole SN, Sikorska K, Schagen van Leeuwen JH, Schreuder HWR, Hermans RHM, de Hingh IHJT, van der Velden J, Arts HJ, Massuger LFAG, et al: Hyperthermic intraperitoneal chemotherapy in ovarian cancer. N Engl J Med. 378:230–240. 2018. View Article : Google Scholar : PubMed/NCBI
17	Jiang H, Tian H, Wang Z, Li B, Chen R, Luo K, Lu S, Nice EC, Zhang W, Huang C, et al: Laser-activatable oxygen self-supplying nanoplatform for efficiently overcoming colorectal cancer resistance by enhanced ferroptosis and alleviated hypoxic microenvironment. Biomater Res. 27:922023. View Article : Google Scholar : PubMed/NCBI
18	Cherkasova V, Ilnytskyy Y, Kovalchuk O and Kovalchuk I: Transcriptome analysis of cisplatin, cannabidiol, and intermittent serum starvation alone and in various combinations on colorectal cancer cells. Int J Mol Sci. 24:147432023. View Article : Google Scholar : PubMed/NCBI
19	Kurien BT and Scofield RH: Western blotting. Methods. 38:283–293. 2006. View Article : Google Scholar : PubMed/NCBI
20	Chen Z, Shi T, Zhang L, Zhu P, Deng M, Huang C, Hu T, Jiang L and Li J: Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 370:153–164. 2016. View Article : Google Scholar : PubMed/NCBI
21	Paumi CM, Chuk M, Snider J, Stagljar I and Michaelis S: ABC transporters in saccharomyces cerevisiae and their interactors: New technology advances the biology of the ABCC (MRP) subfamily. Microbiol Mol Biol Rev. 73:577–593. 2009. View Article : Google Scholar : PubMed/NCBI
22	Porro A, Haber M, Diolaiti D, Iraci N, Henderson M, Gherardi S, Valli E, Munoz MA, Xue C, Flemming C, et al: Direct and coordinate regulation of ATP-binding cassette transporter genes by Myc factors generates specific transcription signatures that significant affect the chemoresistance phenotype of cancer cells. J Biol Chem. 285:19532–19543. 2010. View Article : Google Scholar : PubMed/NCBI
23	Porro A, Iraci N, Soverini S, Diolaiti D, Gherardi S, Terragna C, Durante S, Valli E, Kalebic T, Bernardoni R, et al: c-MYC oncoprotein dictates transcriptional profiles of ATP-binding cassette transporter genes in chronic myelogenous leukemia CD34+ hematopoietic progenitor cells. Mol Cancer Res. 9:1054–1066. 2011. View Article : Google Scholar : PubMed/NCBI
24	Wang Z, Xu Y, Meng X, Watari F, Liu H and Chen X: Suppression of c-Myc is involved in multi-walled carbon nanotubes' down-regulation of ATP-binding cassette transporters in human colon adenocarcinoma cells. Toxicol Appl Pharmacol. 282:42–51. 2015. View Article : Google Scholar : PubMed/NCBI
25	Baluapuri A, Wolf E and Eilers M: Target gene-independent functions of MYC oncoproteins. Nat Rev Mol Cell Biol. 21:255–267. 2020. View Article : Google Scholar : PubMed/NCBI
26	Kleinschmidt MA, Streubel G, Samans B, Krause M and Bauer UM: The protein arginine methyltransferases CARM1 and PRMT1 cooperate in gene regulation. Nucleic Acids Res. 36:3202–3213. 2008. View Article : Google Scholar : PubMed/NCBI
27	Hsu WJ, Chen CH, Chang YC, Cheng CH, TsaI YH and Lin CW: PRMT1 confers resistance to olaparib via modulating MYC signaling in triple-negative breast cancer. J Pers Med. 11:10092021. View Article : Google Scholar : PubMed/NCBI
28	Eberhardt A, Hansen JN, Koster J, Lotta LT Jr, Wang S, Livingstone E, Qian K, Valentijn LJ, Zheng YG, Schor NF and Li X: Protein arginine methyltransferase 1 is a novel regulator of MYCN in neuroblastoma. Oncotarget. 7:63629–63639. 2016. View Article : Google Scholar : PubMed/NCBI
29	Lu W, Yang C, He H and Liu H: The CARM1-p300-c-Myc-Max (CPCM) transcriptional complex regulates the expression of CUL4A/4B and affects the stability of CRL4 E3 ligases in colorectal cancer. Int J Biol Sci. 16:1071–1085. 2020. View Article : Google Scholar : PubMed/NCBI
30	Zhang J, Harnpicharnchai P, Jakovljevic J, Tang L, Guo Y, Oeffinger M, Rout MP, Hiley SL, Hughes T and Woolford JL Jr: Assembly factors Rpf2 and Rrs1 recruit 5S rRNA and ribosomal proteins rpL5 and rpL11 into nascent ribosomes. Genes Dev. 21:2580–2592. 2007. View Article : Google Scholar : PubMed/NCBI
31	Jaremko D, Ciganda M and Williams N: Trypanosoma brucei homologue of regulator of ribosome synthesis 1 (Rrs1) Has direct interactions with essential trypanosome-specific proteins. mSphere. 4:e00453–19. 2019. View Article : Google Scholar : PubMed/NCBI
32	Song J, Ma Z, Hua Y, Xu J, Li N, Ju C and Hou L: Functional role of RRS1 in breast cancer cell proliferation. J Cell Mol Med. 22:6304–6313. 2018. View Article : Google Scholar : PubMed/NCBI
33	Wu XL, Yang ZW, He L, Dong PD, Hou MX, Meng XK, Zhao HP, Wang ZY, Wang F, Baoluri, et al: RRS1 silencing suppresses colorectal cancer cell proliferation and tumorigenesis by inhibiting G2/M progression and angiogenesis. Oncotarget. 8:82968–82980. 2017. View Article : Google Scholar : PubMed/NCBI
34	Li HL, Dong LL, Jin MJ, Li QY, Wang X, Jia MQ, Song J, Zhang SY and Yuan S: A review of the regulatory mechanisms of N-myc on cell cycle. Molecules. 28:11412023. View Article : Google Scholar : PubMed/NCBI
35	Broso F, Gatto P, Sidarovich V, Ambrosini C, De Sanctis V, Bertorelli R, Zaccheroni E, Ricci B, Destefanis E, Longhi S, et al: Alpha-1 adrenergic antagonists sensitize neuroblastoma to therapeutic differentiation. Cancer Res. 83:2733–2749. 2023. View Article : Google Scholar : PubMed/NCBI
36	Yu F, Mou B, Sheng J, Liu J, Qin X and Yu J: DERL3 suppresses colorectal cancer metastasis through negatively regulating MYCN level. Minerva Med. 114:316–322. 2023. View Article : Google Scholar : PubMed/NCBI