AbstractObjective To investigate the effect of lncRNA LINC00958 on the apoptosis and radiosensitivity of colorectal cancer cells and its underlying mechanism. Methods The pcDNA, pcDNA-LINC00958, si-NC, si-LINC00958, miR-NC, and miR-422a plasmids were transfected into SW480 cells and assigned into the pcDNA group, pcDNA-LINC00958 group, si-NC group, si-LINC00958 group, miR-NC group, miR-422a group, respectively. Anti-miR-NC and anti-miR-422a plasmids were co-transfected into SW480 cells with si-LINC00958, and assigned into the si-LINC00958+anti-miR-NC group and si-LINC00958+anti-miR-422a group. miR-NC and miR-422a were transfected into the WT-LINC00958 and MUT-LINC00958 cells, respectively. The fluorescence activity was detected. Cell transfection was performed by liposome method. The expression levels of miR-422a and LINC00958 were measured by qRT-PCR. The expression levels of proteins were detected by Western Blot. Cell apoptosis was assessed by flow cytometry. The radiosensitivity of colorectal cancer cells was evaluated by cell clone formation assay. The fluorescence activity was detected by dual luciferase reporter assay. Results High expression of LINC00958 and low expression of miR-422a were observed in colorectal cancer cells. Inhibition of LINC00958 expression and overexpression of miR-422a could promote cell apoptosis and increase cell radiosensitivity of colorectal cancer cells. LINC00958 could target the regulation of miR-422a expression. Inhibition of miR-422a reversed the effect of inhibiting the expression of LINC00958 on increasing the radiosensitization and promoting cell apoptosis of colorectal cancer cells. Conclusions Inhibition of LINC00958 expression increases the radiosensitivity and promotes the apoptosis of colorectal cancer cells. The mechanism may be related to the regulation of miR-422a, which will provide new targets and new ideas for the treatment of colorectal cancer.
Fund:Henan Medical Science and Technology Research Program (2018020432);Henan Health Science and Technology Talents Overseas Research Project (HWYX2019116)
Liang Hong,Zhang Hui,Zhang Hui. Inhibiting lncRNA LINC00958 expression promotes apoptosis of colorectal cancer cells and increases the radiosensitivity throuth targeting miR-422a[J]. Chinese Journal of Radiation Oncology, 2020, 29(12): 1118-1123.
Liang Hong,Zhang Hui,Zhang Hui. Inhibiting lncRNA LINC00958 expression promotes apoptosis of colorectal cancer cells and increases the radiosensitivity throuth targeting miR-422a[J]. Chinese Journal of Radiation Oncology, 2020, 29(12): 1118-1123.
[1] 王洋,刘珊,蒋永新. 结直肠癌放化疗抵抗功能及机制的研究进展[J]. 肿瘤, 2017, 37(7):795-800. DOI:10.3781/j.issn.1000-7431.2017.55.179. Wang Y, Liu S, Jiang YX. Research progress of chemoradiotherapy resistance and its mechanism in colorectal cancer[J]. Tumor, 2017, 37(7):795-800. DOI:10.3781/j.issn.1000-7431.2017.55.179. [2] 杨野梵,马中华. 长链非编码RNA调控结直肠癌耐药的研究进展[J]. 临床肿瘤学杂志, 2018, 23(5):79-83. DOI:10.3969/j.issn.1009-0460.2018.05.015. Yang YF, Ma ZH. Research progress of long-chain non coding RNA regulating drug resistance of colorectal cancer[J]. J Clin Oncol, 2018, 23(5):79-83. DOI:10.3969/j.issn.1009-0460.2018.05.015. [3] Chen FY, Liu MY, Yu YX, et al. LINC00958 regulated miR-627-5p/YBX2 axis to facilitate cell proliferation and migration in oral squamous cell carcinoma[J]. Cancer Biol Ther, 2019, 20(9):1270-1280. DOI:10.1080/15384047.2019.1617571. [4] Zhao H, Zheng GH, Li GC, et al. Long noncoding RNA LINC00958 regulates cell sensitivity to radiotherapy through RRM2 by binding to microRNA-5095 in cervical cancer[J]. J Cell Physiol, 2019, 234(12):23349-23359. DOI:10.1002/jcp.28902. [5] 张玉虹,李皓,刘阳晨. miRNA 在肿瘤放疗敏感性中的作用及机制[J]. 现代肿瘤医学, 2016, 24(2):314-318. DOI:10.3969/j.issn.1672-4992.2016.02.045. Zhang YH, Li H, Liu YC. The role and mechanism of miRNA in tumor radiosensitivity[J]. Mode Oncol Med, 2016, 24(2):314-318. DOI:10.3969/j.issn.1672-4992.2016.02.045. [6] Li P, Li Q, Zhang Y, et al. MiR-422a targets MAPKK6 and regulates cell growth and apoptosis in colorectal cancer cells[J]. Biomed Pharmacother, 2018, 104:832-840. DOI:10.1016/j.biopha.2018.03.013. [7] Liu M, Xiusheng H, Xiao X, et al. Overexpression of miR-422a inhibits cell proliferation and invasion, and enhances chemosensitivity in osteosarcoma cells[J]. Oncol Rep, 2016, 36(6):3371-3378. DOI:10.3892/or.2016.5182. [8] 彭湃澜,廖斐. 结直肠癌化学性放射增敏剂的研究进展[J]. 疑难病杂志, 2019, 18(3):319-324. DOI:10.3969/j.issn.1671-6450.2019.03.025. Peng PL, Liao F. Research progress of chemoradiosensitizers for colorectal cancer[J]. J Diffi Dis, 2019, 18(3):319-324. DOI:10.3969/j.issn.1671-6450.2019.03.025. [9] 潘雪峰,范乃军,高春芳. LncRNA与结直肠癌诊断治疗的研究进展[J]. 肿瘤学杂志, 2017, 23(2):111-115. DOI:10.11735/j.issn.1671-170X.2017.02. B007. Pan XF, Fan NJ, Gao CF. Research progress of lncrna and diagnosis and treatment of colorectal cancer[J]. J Oncol, 2017, 23(2):111-115. DOI:10.11735/j.issn.1671-170X.2017.02. B007. [10] Yang XD, Xu HT, Xu XH, et al. Knockdown of long non-coding RNA HOTAIR inhibits proliferation and invasiveness and improves radiosensitivity in colorectal cancer[J]. Oncol Rep, 2016, 35(1):479-487. DOI:10.3892/or.2015.4397. [11] 付玉娟,殷涛,倪猛,等. XIST/miRNA-34a信号轴调控结直肠癌细胞SW480放疗敏感性的机制研究[J]. 癌症进展, 2019, 17(6):661-665. DOI:10.11877/j.issn.1672-1535.2019.17.06.10. Fu YJ, Yin T, Ni M, et al. Study on the mechanism of Xist/mirna-34a signal axis regulating the radiosensitivity of colorectal cancer SW480 cells[J]. Cancer Prog, 2019, 17(6):661-665. DOI:10.11877/j.issn.1672-1535.2019.17.06.10. [12] Seitz AK, Christensen LL, Cheristensen E, et al. Profiling of long non-coding RNAs identifies LINC00958 and LINC01296 as candidate oncogenes in bladder cancer[J]. Sci Rep, 2017, 7(1):395. DOI:10.1038/s41598-017-00327-0. [13] Guo E, Liang C, He X, et al. Long noncoding RNA LINC00958 accelerates gliomagenesis through regulating miR-203/CDK2[J]. DNA Cell Biol, 2018, 37(5):465-472. DOI:10.1089/dna.2018.4163. [14] 朱玥荃, 熊凯, 温杰, 等. MicroRNAs与结直肠癌辐射敏感性的关系及作用机制[J]. 中华放射医学与防护杂志, 2016, 36(10):780-784. DOI:10.3760/cma.j.issn.0254-5098.2016.10.014. Zhu YQ, Xiong K, Wen J, et al. Relationship between microRNAs and radiosensitivity of colorectal cancer and its mechanism of action[J]. Chin J Radipl Med Protect, 2016, 36(10):780-784. DOI:10.3760/cma.j.issn.0254-5098.2016.10.014. [15] 张晓槟. 反义microRNA-221对结直肠癌细胞放射敏感性的影响及相关机制[D]. 广州:南方医科大学, 2013. Zhang XB. Effect of antisense microrna-221 on radiosensitivity of colorectal cancer cells and related mechanisms[D]. Guangzhou:Southern Medical University, 2013. [16] 林水苗. MiR-124通过靶向PRRX1调节结直肠癌辐射敏感性[D]. 广州:南方医科大学, 2016. Lin SM. MiR-124 regulates radiosensitivity of colorectal cancer by targeting prrx1[D]. Guangzhou:Southern Medical University, 2016. [17] Wei WT, Nian XX, Wang SY, et al. miR-422a inhibits cell proliferation in colorectal cancer by targeting AKT1 and MAPK1[J]. Cancer Cell Int, 2017,17:91. DOI:10.1186/s12935-017-0461-3. [18] Zheng GX, Qu AL, Yang YM, et al. miR-422a is an independent prognostic factor and functions as a potential tumor suppressor in colorectal cancer[J]. World J Gastroenterol, 2016, 22(24):5589-5597. DOI:10.3748/wjg.v22.i24.5589. [19] Zhou Z, Lin Z, He Y, et al. The long noncoding RNA D63785 regulates chemotherapy sensitivity in human gastric cancer by targeting miR-422a[J]. Mol Ther Nucleic Acids, 2018,12:405-419. DOI:10.1016/j.omtn.2018.05.024. [20] Zhu SP, Wang JY, Wang XG, et al. Long intergenic non-protein coding RNA 00858 functions as a competing endogenous RNA for miR-422a to facilitate the cell growth in non-small cell lung cancer[J]. Aging, 2017, 9(2):475-485. DOI:10.18632/aging.101171.