title: MicroRNA target for MACC1 and CYR61 to inhibit tumor growth in mice with colorectal cancer.
abstract: Cysteine-rich protein 61 (CYR61) and metastasis associated in colon cancer (MACC1) protein promoted human colorectal cancer (CRC) cell metastasis and closely related to the patient's prognosis in colorectal cancer. The purpose of this article is to investigate whether CYR61 and MACC1 can serve as dual potential targets for gene therapy of human CRC. In this study, microRNA (miRNA) targeting for both CYR61 and MACC1 was used to investigate the mechanism and therapeutic effects for CRC cells and mice with CRC. We observed that silencing miRNA for CYR61 and MACC1 inhibited the epithelial-mesenchymal transition (EMT) process, and co-treatment strengthened this effect. MTT assay showed that the growth of colorectal tumor cells was decreased due to miRNA treatment. Apoptosis assay revealed that miRNA for CYR61 and MACC1 promoted CRC cells apoptotic. The animals' study results showed that the expression levels of CYR61 and MACC1 were significantly decreased after miRNA-100 and miRNA-143 treatment, respectively. The expression levels of apoptosis-promoting protein were increased significantly after treatment with miRNA-100 and miRNA-143, which suggested that both miRNA-100 and miRNA-143 may induce apoptosis by mitochondria-dependent pathway. In addition, metastasis and invasion assays showed that miRNA-100 and miRNA-143 treatment inhibited obviously migratory and invasive abilities of CRC cells. Furthermore, our data also showed that the tumor growth was significantly inhibited and survival rate of tumor-bearing mice was greatly improved by common treatments of miRNA-100 and miRNA-143. In conclusion, the abilities of apoptosis, metastasis, and invasion in CRC tumor cells were significantly suppressed by miRNA-100 and miRNA-143 targeting CYR61 and MACC1, respectively. As a result, CYR61 and MACC1 may serve as potential targets for gene therapy in human CRC treatments.
authors: Department of Gastrointestinal Surgery, First Affiliated Hospital of Hebei Medical University, No. 89, Donggang Road, Shijiazhuang, 050031, China.
authors: Guiqi
authors: G
authors: Wang
authors: Department of Gastrointestinal Surgery, First Affiliated Hospital of Hebei Medical University, No. 89, Donggang Road, Shijiazhuang, 050031, China. gujingfenpro@163.com.
authors: Jingfeng
authors: J
authors: Gu
authors: Department of Gastrointestinal Surgery, First Affiliated Hospital of Hebei Medical University, No. 89, Donggang Road, Shijiazhuang, 050031, China.
authors: Yingchao
authors: Y
authors: Gao
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D055515:Cysteine-Rich Protein 61 / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; C501848:CCN1 protein, human; D055515:Cysteine-Rich Protein 61; C544162:MACC1 protein, human; D035683:MicroRNAs; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors
keywords: Apoptosis; CYR 61; Colorectal cancer; MACC1; MicroRNA