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ShRNA-induced silencing of Ras-related C3 botulinum toxin substrate 1 inhibits the proliferation of colon cancer cells through upregulation of BAD and downregulation of cyclin D1.

ABSTRACT: Ras-related C3 botulinum toxin substrate 1 (RAC1) is a member of the Rho family of small GTPases. Recent studies have reported that RAC1 serves an important role in colon cancer cell proliferation. The present study aimed to investigate the effects of RAC1 knockdown on cell proliferation, cell cycle progression and apoptosis of colon cancer cells. Lentivirus?mediated short hairpin RNA (shRNA) was used to knockdown RAC1 expression in colon cancer cell lines, and cell proliferation, apoptosis, cell cycle progression were evaluated by MTT assays and flow cytometry. The differences in mRNAs expression were identified between RAC1-knockdown cells and control cells using a mRNA microarray, following which quantitative PCR (qPCR) and western blot were employed to confirm the results of the mRNA microarray. The proliferative ability of colon cancer cells was significantly decreased following RAC1 knockdown, and RAC1 knockdown increased the apoptotic rate and enhanced cell cycle arrest at G1 phase in colon cancer cells. In addition, >1,200 known genes were demonstrated to be involved in RAC1?associated tumorigenic functions in SW620 colon cancer cells, as determined by gene chip analysis; these genes were associated with cell proliferation, cell cycle, apoptosis and metastasis. Furthermore, western blot analysis indicated that cyclin D1 was downregulated, whereas B?cell lymphoma 2?associated agonist of cell death (BAD) was upregulated following RAC1 knockdown in colon cancer cells. In conclusion, RAC1 silencing may suppress the proliferation of colon cancer cells by inducing apoptosis and cell cycle arrest. In addition, a large number of genes were revealed to be involved in the process, including BAD, which was upregulated and cyclin D1, which was downregulated. Further studies on these differentially expressed genes may provide a better understanding of the potential roles of RAC1 in colon carcinogenesis.

SUBMITTER: Huang YS

PROVIDER: S-EPMC5819921 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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shRNA-induced silencing of Ras-related C3 botulinum toxin substrate 1 inhibits the proliferation of colon cancer cells through upregulation of BAD and downregulation of cyclin D1.

Huang You-Sheng YS Jie Na N Zhang Yi-Xin YX Zou Ke-Jian KJ Weng Yang Y

International journal of molecular medicine 20171222 3

Ras-related C3 botulinum toxin substrate 1 (RAC1) is a member of the Rho family of small GTPases. Recent studies have reported that RAC1 serves an important role in colon cancer cell proliferation. The present study aimed to investigate the effects of RAC1 knockdown on cell proliferation, cell cycle progression and apoptosis of colon cancer cells. Lentivirus‑mediated short hairpin RNA (shRNA) was used to knockdown RAC1 expression in colon cancer cell lines, and cell proliferation, apoptosis, cel ...[more]

PMID: 29286138

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Project description:Thyroid cancer (TC) is a frequently occurring malignant tumor with a rising steadily incidence. microRNA (miRNA/miR)‑193a‑3p is an miRNA that is associated with tumors, playing a crucial role in the genesis and progression of various cancers. However, the expression levels of miR‑193a‑3p and its molecular mechanisms in TC remain to be elucidated. The present study aimed to probe the expression of miR‑193a‑3p and its clinical significance in TC, including its underlying molecular mechanisms. Microarray and RNA sequencing data gathered from three major databases, specifically Gene Expression Omnibus (GEO), ArrayExpress and The Cancer Genome Atlas (TCGA) databases, and the relevant data from the literature were used to examine miR‑193a‑3p expression. Meta‑analysis was also conducted to evaluate the association between clinicopathological parameters and miR‑193a‑3p in 510 TC and 59 normal samples from the TCGA database. miRWalk 3.0, and the TCGA and GEO databases were used to predict the candidate target genes of miR‑193a‑3p. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes and protein‑protein interaction network enrichment analyses were conducted by using the predicted candidate target genes to investigate the underlying carcinogenic mechanisms. A dual luciferase assay was performed to validate the targeting regulatory association between the most important hub gene cyclin D1 (CCND1) and miR‑193a‑3p. miR‑193a‑3p expression was considerably downregulated in TC compared with in the non‑cancer controls (P<0.001). The area under the curve of the summary receiver operating characteristic was 0.80. Downregulation of miR‑193a‑3p was also significantly associated with age, sex and metastasis (P=0.020, 0.044 and 0.048, respectively). Bioinformatics analysis indicated that a low miR‑193a‑3p expression may augment CCND1 expression to affect the biological processes of TC. In addition, CCND1, as a straightforward target, was validated through a dual luciferase assay. miR‑193a‑3p and CCND1 may serve as prognostic biomarkers of TC. Finally, miR‑193a‑3p may possess a crucial role in the genesis and progression of TC by altering the CCND1 expression.

Dataset Information

ShRNA-induced silencing of Ras-related C3 botulinum toxin substrate 1 inhibits the proliferation of colon cancer cells through upregulation of BAD and downregulation of cyclin D1.

Publications

shRNA-induced silencing of Ras-related C3 botulinum toxin substrate 1 inhibits the proliferation of colon cancer cells through upregulation of BAD and downregulation of cyclin D1.

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