microRNA-96 promotes occurrence and progression of colorectal cancer via regulation of the AMPK alpha 2-FTO-m6A/MYC axis

Yue, Caifeng1; Chen, Jierong2; Li, Ziyue3; Li, Laisheng4; Chen, Jugao5; Guo, Yunmiao6

2020-11-12

10.1186/s13046-020-01731-7

JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH   影响因子和分区

1756-9966

1756-9966

Background Colorectal cancer (CRC) is one of the frequently occurred malignancies in the world. To date, several onco-microRNAs (miRNAs or miRs), including miR-96, have been identified in the pathogenesis of CRC. In the present study, we aimed to corroborate the oncogenic effect of miR-96 on CRC and to identify the specific mechanisms related to AMPK alpha 2/FTO/m6A/MYC. Methods RT-qPCR and Western blot analysis were performed to examine the expression pattern of miR-96, AMPK alpha 2, FTO and MYC in the clinical CRC tissues and cells. The relationship between miR-96 and AMPK alpha 2 was then predicted using in silico analysis and identified by dual-luciferase reporter assay. Gain- or loss-of-function approaches were manipulated to evaluate the modulatory effects of miR-96, AMPK alpha 2, FTO and MYC on cell growth, cycle progression and apoptosis. The mechanism of FTO-mediated m6A modification of MYC was analyzed via Me-RIP and PAR-CLIP analysis. The mediatory effects of miR-96 antagomir on cancerogenesis were validated in vivo. Results miR-96, FTO and MYC were upregulated, while AMPK alpha 2 was downregulated in CRC tissues and cells. miR-96 could down-regulate AMPK alpha 2, which led to increased expression of FTO and subsequent upregulated expression of MYC via blocking its m6A modification. This mechanism was involved in the pro-proliferative and anti-apoptotic roles of miR-96 in CRC cells. Besides, down-regulation of miR-96 exerted inhibitory effect on tumor growth in vivo. Conclusions Taken together, miR-96 antagomir could potentially retard the cancerogenesis in CRC via AMPK alpha 2-dependent inhibition of FTO and blocking FTO-mediated m6A modification of MYC, highlighting novel mechanisms associated with colorectal cancerogenesis.

Colorectal cancer microRNA-96 m6A modification AMPKα 2 FTO MYC

SCI

英语

通讯

National Natural Science Foundation of China[81602416][81602691] ; Guangzhou Science and Technology Projects[201803010094]

Oncology

Oncology

WOS:000589072100001

BMC

CLINICAL MEDICINE

Web of Science

1.Guangdong Med Univ, Zhanjiang Cent Hosp, Cent Peoples Hosp Zhanjiang, Dept Lab Med, 236 Yuanzhu Rd, Zhanjiang 524045, Peoples R China
2.Guangdong Acad Med Sci, Guangdong Prov Peoples Hosp, Div Lab Med, Guangzhou 510080, Peoples R China
3.Guangzhou Med Univ, Guangzhou Women & Childrens Med Ctr, Guangzhou 510623, Peoples R China
4.Sun Yat Sen Univ, Dept Lab Med, Affiliated Hosp 1, Guangzhou 510080, Peoples R China
5.Southern Univ Sci & Technol, Jinan Univ, Affiliated Hosp 1, Dept Oncol,Shenzhen Peoples Hosp,Clin Med Coll 2, 3046 Shennan East Rd, Shenzhen 518020, Guangdong, Peoples R China
6.Guangdong Med Univ, Zhanjiang Cent Hosp, Zhanjiang Cent Peoples Hosp Zhanjiang, Clin Res Inst Zhanjiang, 236 Yuanzhu Rd, Zhanjiang 524045, Guangdong, Peoples R China

Yue, Caifeng,Chen, Jierong,Li, Ziyue,et al. microRNA-96 promotes occurrence and progression of colorectal cancer via regulation of the AMPK alpha 2-FTO-m6A/MYC axis[J]. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH,2020,39(1).

Yue, Caifeng,Chen, Jierong,Li, Ziyue,Li, Laisheng,Chen, Jugao,&Guo, Yunmiao.(2020).microRNA-96 promotes occurrence and progression of colorectal cancer via regulation of the AMPK alpha 2-FTO-m6A/MYC axis.JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH,39(1).

Yue, Caifeng,et al."microRNA-96 promotes occurrence and progression of colorectal cancer via regulation of the AMPK alpha 2-FTO-m6A/MYC axis".JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH 39.1(2020).