Knockdown of astrocyte elevated gene-1 inhibits tumor growth and modifies microRNAs expression profiles in human colorectal cancer cells.
Astrocyte elevated gene-1 (AEG-1), upregulated in various types of malignancies including colorectal cancer (CRC), has been reported to be associated with the carcinogenesis. MicroRNAs (miRNAs) are widely involved in the initiation and progression of cancer. However, the functional significance of AEG-1 and the relationship between AEG-1 and microRNAs in human CRC remains unclear. The aim of this study was to investigate whether AEG-1 could serve as a potential therapeutic target of human CRC and its possible mechanism. We adopted a strategy of ectopic overexpression or RNA interference to upregulate or downregulate expression of AEG-1 in CRC models. Their phenotypic changes were analyzed by Western blot, MTT and transwell matrix penetration assays. MicroRNAs expression profiles were performed using microarray analysis followed by validation using qRT-PCR. Knockdown of AEG-1 could significantly inhibit colon cancer cell proliferation, colony formation, invasion and promotes apoptosis. Conversely, upregulation of AEG-1 could significantly enhance cell proliferation, invasion and reduced apoptisis. AEG-1 directly contributes to resistance to chemotherapeutic drug. Targeted downregulation of AEG-1 might improve the expression of miR-181a-2(∗), -193b and -193a, and inversely inhibit miR-31 and -9(∗). Targeted inhibition of AEG-1 can lead to modification of key elemental characteristics, such as miRNAs, which may become a potential effective therapeutic strategy for CRC.
East Department of Gastroenterology, Institute of Geriatrics, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, PR China; Southern Medical University, Guangzhou, Guangdong 510515, PR China.
Sujun
S
Huang
East Department of Gastroenterology, Institute of Geriatrics, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, PR China. Electronic address: wubinwengd@aliyun.com.
Binwen
B
Wu
East Department of Gastroenterology, Institute of Geriatrics, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, PR China.
Dongfeng
D
Li
East Department of Gastroenterology, Institute of Geriatrics, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, PR China.
Weihong
W
Zhou
East Department of Gastroenterology, Institute of Geriatrics, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, PR China.
Gang
G
Deng
East Department of Gastroenterology, Institute of Geriatrics, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, PR China.
Kaijun
K
Zhang
East Department of Gastroenterology, Institute of Geriatrics, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, PR China.
Youjia
Y
Li
D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000235:genetics*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology*; D017931:DNA Primers; D005472:Fluorouracil / Q000494:pharmacology; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D006801:Humans; D008565:Membrane Proteins; D035683:MicroRNAs / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D016601:RNA-Binding Proteins; D060888:Real-Time Polymerase Chain Reaction
D015815:Cell Adhesion Molecules; D017931:DNA Primers; C483039:MTDH protein, human; D008565:Membrane Proteins; D035683:MicroRNAs; D016601:RNA-Binding Proteins; D005472:Fluorouracil
AEG-1; CRC; Chemoresistance; MicroRNAs; Proliferation