MiR-138 promotes apoptosis of colon cancer cells by targeting SIRT1

Yang YANG; Wenli PENG

doi:10.16016/j.1000-5404.202104063

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MiR-138 promotes apoptosis of colon cancer cells by targeting SIRT1

Basic Medicine | 更新时间：2026-01-09

- MiR-138 promotes apoptosis of colon cancer cells by targeting SIRT1
- Journal of Third Military Medical University Vol. 43, Issue 19, Pages: 1877-1883(2021)
- 作者机构：
  
  400030 重庆，重庆大学附属肿瘤医院，肿瘤转移与个体化诊治转化研究重庆市重点实验室
- 作者简介：
- 基金信息：
- DOI：10.16016/j.1000-5404.202104063
  CLC： R394.3;R73-362;R735.35
- Received：10 April 2021，
  
  Revised：2021-07-08，
  
  Published：15 October 2021
- 稿件说明：
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Yang YANG, Wenli PENG. MiR-138 promotes apoptosis of colon cancer cells by targeting SIRT1[J]. Journal of Third Military Medical University, 2021, 43(19): 1877-1883.
DOI：

Yang YANG, Wenli PENG. MiR-138 promotes apoptosis of colon cancer cells by targeting SIRT1[J]. Journal of Third Military Medical University, 2021, 43(19): 1877-1883. DOI： 10.16016/j.1000-5404.202104063.

摘要

目的

探讨miR-138在结肠癌细胞中通过调控沉默信息调节因子2相关酶1(silent mating type information regulation 2 homolog-1，SIRT1)参与细胞凋亡的机制。

方法

采用RT-qPCR检测miR-138在结肠癌细胞株HCT116、SW480、Caco-2、HT29、SW1116中的表达。构建荧光素酶报告质粒，双荧光素酶实验验证靶标分子。将miR-138 mimics(类似物)、miR-138 inhibitors(抑制物)和miR-138 NC(阴性对照)分别转染至HT29、Caco-2细胞，RT-qPCR和Western bolt检测处理前后HCT116细胞中miR-138、SIRT1、Caspase-3及Bcl-2的表达；流式细胞仪检测HT29、Caco-2细胞凋亡情况。

结果

miR-138在结肠癌细胞Caco-2中表达水平最低，在HT29细胞中表达水平最高。双荧光素酶实验验证结果显示: 在HT29细胞中，SIRT1为miR-138的靶标分子，miR-138可在mRNA及蛋白水平抑制SIRT1的表达。miR-138 mimics转染至Caco-2细胞后，其SIRT1、Bcl-2表达显著降低(

0.05)，Caspase-3表达显著升高(

0.05)，细胞凋亡增加(

0.05)；而miR-138 inhibitors转染至HT29细胞后，其SIRT1、Bcl-2表达显著升高(

0.05)，Caspase-3表达显著降低(

0.05)，细胞凋亡减少(

0.05)。

结论

miR-138可通过影响其靶标分子SIRT1的表达进而参与结肠癌细胞凋亡水平的调控。

Abstract

Objective

To investigate the mechanism of miR-138 involving in the apoptosis of colon cancer cells by regulating SIRT1.

Methods

RT-qPCR was used to detect the expression of miR-138 in colon cancer cell lines HCT 116

SW480

Caco-2

HT29 and SW1116. The luciferase reporter plasmid was constructed and the target molecule was verified by double luciferase assay. MiR-138 mimics

miR-138 inhibitor and miR-138 NC (negative control) were transfected into HT29 and Caco-2 cells

respectively. The expression levels of miR-138

SIRT1

Caspase-3 and Bcl-2 in the cells of each group were detected by RT-qPCR and Western blotting

and the apoptosis of Caco-2 and HT29 cells was detected by flow cytometry.

Results

MiR-138 showed the lowest expression level in Caco-2 cells and the highest expression level in HT29 cells. SIRT1 was identified as a direct target of miR-138 in HT29 cells

and miR-138 inhibited SIRT1 expression at both mRNA and protein levels. After transfection of miR-138 mimics into Caco-2 cells

the expression of SIRT1 and Bcl-2 was significantly dec

reased (

0.05)

Caspase-3 was enhanced (

0.05)

meanwhile the apoptosis was increased (

0.05). Whereas after miR-138 inhibitor transfected into HT29 cells

the expression of SIRT1 and Bcl-2 was obviously increased (

0.05)

Caspase-3 was decreased (

0.05)

and the apoptosis reduced (

0.05).

Conclusion

MiR-138 promotes apoptosis of colon cancer cells by regulating the expression of its target SIRT1.

关键词

Keywords

references

DEWANJI A, JEON J, MEZA R, et al . Number and size distribution of colorectal adenomas under the multistage clonal expansion model of cancer[J ] . PLoS Comput B iol, 2011, 7(10): e1002213. DOI:10.1371/journal.pcbi.1002213.

PENG F, HUANG Y, LI M Y, et al . Dissecting characteristics and dynamics of differentially expressed proteins during multistage carcinogenesis of human colorectal cancer[J ] . World J Gastroenterol, 2016, 22(18): 4515-4528. DOI:10.3748/wjg.v22.i18.4515.

STEINFELD B, SCOTT J, VILANDER G, et al . The role of lean process improvement in implementation of evidence-based practices in behavioral health care[J ] . J Behav Health Serv Res, 2015, 42(4): 504-518. DOI:10.1007/s11414-013-9386-3.

MILLER K D, NOGUEIRA L, MARIOTTO A B, et al . Cancer treatment and survivorship statistics, 2019[J ] . CA Cancer J Clin, 2019, 69(5): 363-385. DOI:10.3322/caac.21565.

KESHAVARZI M, SORAYAYI S, JAFAR REZAEI M, et al . MicroRNAs-based imaging techniques in cancer diagnosis and therapy[J ] . J Cell Biochem, 2017, 118(12): 4121-4128. DOI:10.1002/jcb.26012.

ANASTASIADOU E, JACOB L S, SLACK F J. Non-coding RNA networks in cancer[J]. Nat Rev Cancer, 2018, 18(1): 5-18. DOI:10.1038/nrc.2017.99.

CHEN L Y, ZHI Z, WANG L, et al . NSD2 circular RNA promotes metastasis of colorectal cancer by targeting miR-199b-5p-mediated DDR1 and JAG1 signalling[J ] . J Pathol, 2019, 248(1): 103-115. DOI:10.1002/path.5238.

XU Y, PAN Z G, SHU L, et al . Podocalyxin-like, targeted by miR-138, promotes colorectal cancer cell proliferation, migration, invasion and EMT[J ] . Eur Rev Med Pharmacol Sci, 2018, 22(24): 8664-8674. DOI:10.26355/eurrev_201812_16631.

BABAEI K, SHAMS S, KEYMORADZADEH A, et al . An insight of microRNAs performance in carcinogenesis and tumorigenesis; an overview of cancer therapy[J ] . Life Sci, 2020, 240: 117077. DOI:10.1016/j.lfs.2019.117077.

WANG Y, ZHANG D, LI Y, et al . MiR-138 suppresses the PDK1 expression to decrease the oxaliplatin resistance of colorectal cancer[J ] . Oncotargets Ther, 2020, 13: 3607-3618. DOI:10.2147/OTT.S242929.

ZHANG X L, XU L L, WANG F. Hsa_circ_0020397 regulates colorectal cancer cell viability, apoptosis and invasion by promoting the expression of the miR-138 targets TERT and PD-L1[J]. Cell Biol Int, 2017, 41(9): 1056-1064. DOI:10.1002/cbin.10826.

YE Z T, FANG B M, PAN J W, et al . miR-138 suppresses the proliferation, metastasis and autophagy of non-small cell lung cancer by targeting Sirt1[J ] . Oncol Rep, 2017, 37(6): 3244-3252. DOI:10.3892/or.2017.5619.

XU J, LI L, YUN H F, et al . MiR-138 promotes smooth muscle cells proliferation and migration in db/db mice through down-regulation of SIRT1[J ] . Biochem Biophys Res Commun, 2015, 463(4): 1159-1164. DOI:10.1016/j.bbrc.2015.06.076.

LUO J, CHEN P, XIE W, et al . MicroRNA-138 inhibits cell proliferation in hepatocellular carcinoma by targeting Sirt1[J ] . Oncol Rep, 2017, 38(2): 1067-1074.

ALVES-FERNANDES D K, JASIULIONIS M G. The role of SIRT1 on DNA damage response and epigenetic alterations in cancer[J]. Int J Mol Sci, 2019, 20(13): 3153. DOI:10.3390/ijms20133153.

QIANG L, SAMPLE A, LIU H, et al . Epidermal SIRT1 regulates inflammation, cell migration, and wound healing[J ] . Sci Rep, 2017, 7(1): 1-10. DOI:10.1038/s41598-017-14371-3.

SUBRAMANIYAN B, KUMAR V, MATHAN G. Effect of sodium salt of Butrin, a novel compound isolated from Butea monosperma flowers on suppressing the expression of SIRT1 and Aurora B kinase-mediated apoptosis in colorectal cancer cells[J]. Biomed Pharmacother, 2017, 90: 402-413. DOI:10.1016/j.biopha.2017.03.086.

PAN J H, ZHOU H, ZHU S B, et al . Nicotinamide phosphoribosyl transferase regulates cell growth via the Sirt1/P53 signaling pathway and is a prognosis marker in colorectal cancer[J ] . J Cell Physiol, 2019, 234(4): 4385-4395. DOI:10.1002/jcp.27228.

NAGATA S, TANAKA M. Programmed cell death and the immune system[J]. Nat Rev Immunol, 2017, 17(5): 333-340. DOI:10.1038/nri.2016.153.

LEGRAND A J, KONSTANTINOU M, GOODE E F, et al . The diversification of cell death and immunity: memento mori[J ] . Mol Cell, 2019, 76(2): 232-242. DOI:10.1016/j.molcel.2019.09.006.

WANG C P, SUN X, QIU Z, et al . MiR-138-5p exacerbates hypoxia/reperfusion-induced heart injury through the inactivation of SIRT1-PGC-1α[J ] . Inflamm Res, 2019, 68(10): 867-876. DOI:10.1007/s00011-019-01268-2.

CHEN Y, FANG L, ZHANG J L, et al . Blockage of glyoxalase I inhibits colorectal tumorigenesis and tumor growth via upregulation of STAT1, p53, and bax and downregulation of c-myc and bcl-2[J ] . Int J Mol Sci, 2017, 18(3): 570. DOI:10.3390/ijms18030570..

MELUCCI E, COSIMELLI M, CARPANESE L, et al . Decrease of survivin, p53 and Bcl-2 expression in chemorefractory colorectal liver metastases may be predictive of radiosensivity radiosensivity after radioembolization with yttrium-90 resin microspheres[J ] . J Exp Clin Cancer Res, 2013, 32: 13. DOI:10.1186/1756-9966-32-13.

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