miR-106b enhances cell radioresistance by targeting PTEN in colorectal carcinoma
Zhang Yuqin1, Zheng Lin2, Ding Yi1
1Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China, 2Department of Pathology, School of Basic Medical Sciences, Southern Medical University/Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
Abstract:Objective To investigate the role of miR-106b in the cell radioresistance in colorectal carcinoma (CRC), and unravel the underlying mechanism. Methods The CRC cell lines stably overexpressing and interfering miR-106b were established. The effect of miR-106b upon the CRC cell radiosensitivity was evaluated by cell radiation, immunofluorescence and colony formation assay. The expression levels of Caspase-3 and γ-H2AX were detected by Western blot. The target genes of miR-106b were identified by bioinformatics prediction, which were further validated by dual luciferase assay, fluorescence quantitative PCR and Western blot. The CRC cell lines stably overexpressing miR-106b were transfected with pCDNA3.0-PTEN. The changes of CRC cell radiosensitivity were investigated. Whether miR-106b could increase the radioresistance of CRC cells by targeting PTEN was clarified. Results Compared with the control group (miR-ctr group), the cell surviving fraction was significantly elevated (P<0.05), the radioresistance (P<0.05) was considerably enhanced and the expression levels of Caspase-3 and γ-H2AX were significantly down-regulated (both P<0.05) in the miR-106b overexpression group. PTEN up-regulation in CRC cell lines stably overexpressing miR-106b could reverse the radioresistance induced by miR-106b. Conclusion miR-106b can induce CRC cell radioresistance by inhibiting PTEN, prompting that miR-106b-PTEN might provide theoretical evidence for relevant targets which can enhance the clinical efficacy of radiotherapy.
[1] Sun MF, Liu JL, Chai YQ, et al. A 3D CdTe QDs-DNA nano-reticulation as highly efficient electrochemiluminescent emitter for ultrasensitive detection of microrna from cancer cells[J]. Anal Chem, 2019, 91(12):7765-7773. DOI:10.1021/acs.analchem.9b01185. [2] Lei L, Zhao XJ, Liu SZ, et al. MicroRNA-3607 inhibits the tumorigenesis of colorectal cancer by targeting DDI2 and regulating the DNA damage repair pathway[J]. Apoptosis, 2019, 24(7-8):662-672. DOI:10.1007/s10495-019-01549-5. [3] Yuan WB, Zhou R, Wang JZ, et al. Circular RNA Cdr1as sensitizes bladder cancer to cisplatin by upregulating APAF1 expression through miR-1270 inhibition[J]. Mol Oncol, 2019, 13(7):1559-1576. DOI:10.1002/1878-0261.12523. [4] Cheng L, Shi XZ, Huo DM, et al. MiR-449b-5p regulates cell proliferation, migration and radioresistance in cervical cancer by interacting with the transcription suppressor FOXP1[J]. Eur J Pharmacol, 2019, 856:172399. DOI:10.1016/j.ejphar.2019.05.028. [5] Zhang TT, Xue X, Peng HX. Therapeutic delivery of miR-29b enhances radiosensitivity in cervical cancer[J]. Mol Ther, 2019, 27(6):1183-1194. DOI:10.1016/j.ymthe.2019.03.020. [6] Oh JS, Kim JJ, Byun JY, et al. Lin28-let7 modulates radiosensitivity of human cancer cells with activation of K-Ras[J]. Int J Radiati Oncol Biol Phys, 2010, 76(1):5-8. DOI:10.1016/j.ijrobp.2009.08.028. [7] Arora H, Qureshi R, Jin S, et al. miR-9 and let-7g enhance the sensitivity to ionizing radiation by suppression of NFκB1[J]. Exp Mol Med, 2011, 43(5):298-304. DOI:10.3858/emm.2011.43.5.031. [8] Yan D, Ng WL, Zhang XM, et al. Targeting DNA-PKcs and ATM with miR-101 sensitizes tumors to radiation[J]. PLoS one, 2010, 5(7):e11397. DOI:10.1371/JOURNAL. PONE.0011397. [9] Chen G, Zhu W, Shi D, et al. MicroRNA-181a sensitizes human malignant glioma U87mg cells to radiation by targeting Bcl-2[J]. Oncol Rep, 2010, 23(4):997-1003. DOI:10.3892/OR_00000725. [10] Sun K, Jia ZK, Duan RR, et al. Long non-coding RNA XIST regulates miR-106b-5p/P21 axis to suppress tumor progression in renal cell carcinoma[J]. Biochem Biophys Res Commun, 2019, 510(3):416-420. DOI:10.1016/j.bbrc.2019.01.116.