[Relationship between the expression level of miR-29c and biological behavior of gastric cancer].
OBJECTIVE
To study the function and clinicopathological significance of RNA-29c (miR-29c) in the carcinogenesis and development of gastric cancer.


METHODS
MicroRNA microarray was applied to assess the miRNAs expression profile of gastric cancer. Quantitative real-time PCR was used to detect the expression of miR-29c in 64 cases of gastric cancer tissues and corresponding normal gastric epithelium, as well as cell lines GES-1, BGC-823 and SGC-7901 cells. MTT assay and flow cytometry were applied to detect the effects of forced expression of miR-29c in gastric cancer BGC-823 cells including cell proliferation, apoptosis, cell cycle and drug sensitivity. Quantitative real-time PCR, Western blot and luciferase reporter assay were used to explore the targeted relationship between miR-29c and myeloid cell leukemia-1 (Mcl-1).


RESULTS
Compared with normal gastric epithelium, seven microRNAs (miR-374b*, miRPlus-E1212, miR-338-5p, miR-297, miR-21, miR-135b, miR-18a) were significantly up-regulated more than 2-folds, and nine microRNAs (miR-29b-2*, miR-1260, miRPlus-E1241, miR-S1-5p, miR-148a, miR-29c, miR-647, miR-196b*, ebv-miR-BART5) were significantly down-reguated in gastric cancer tissues. The average expression level of miR-29c in gastric cancer tissues was 0.70 ± 0.34 and in corresponding normal epithelium was 1.00 ± 0.06 (P < 0.05). miR-29c expression was related to tumor size, lymph node metastasis, clinical stage, Laurén classification, Borrmann classification and Ming classification (P < 0.05). The poorer differentiation degree of gastric cell lines, the lower was miR-29c expression level (P < 0.05). Overexpression of miR-29c in gastric cancer BGC-823 cells suppressed cell proliferation, stimulated cell apoptosis, induced cell cycle arrest in S phase and increased the chemotherapy sensitivity to drug docetaxel (all were P < 0.05). The average expression level of Mcl-1 mRNA in gastric cancer tissues was 3.47 ± 1.34 and corresponding epithelialium was 1.00 ± 0.20 (P < 0.05). The expression level of miR-29c was negatively related with that of Mcl-1 mRNA in gastric cancer tissues. miR-29c directly targeted to regulation of Mcl-1 expression.


CONCLUSIONS
There are special miRNA expression profile in gastric cancer. The expression of miR-29c is closely related to biological behavior of human gastric cancer. miR-29c is involved in targeted regulation of Mcl-1, and may be one of mechanisms of the carcinogenesis of gastric cancer.
Department of Surgical Oncology, Xiamen Cancer Center, First Affiliated Hospital of Xiamen University, Xiamen 361003, China.
Xiao-qiu
XQ
Ma
Lin-pei
LP
Wang
Qi-cong
QC
Luo
Jian-chun
JC
Cai
D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis; D059447:Cell Cycle Checkpoints; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D046228:Microarray Analysis; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics / Q000378:metabolism*; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D043823:Taxoids / Q000627:therapeutic use; D059467:Transcriptome; D047368:Tumor Burden
D000970:Antineoplastic Agents; C579095:MCL1 protein, human; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D012333:RNA, Messenger; D043823:Taxoids; D000077143:Docetaxel