Microribonucleic Acid-15a-5p Alters Adriamycin Resistance in Breast Cancer Cells by Targeting Cell Division Cycle-Associated Protein 4.

OBJECTIVE: Although chemotherapy is one of the first line clinical treatment of tumors, the efficacy of chemotherapy has been severely restricted by the frequent occurrence of drug resistance phenomenon. Multiple studies found that miRNAs can regulate the chemosensitivity of tumor cells. Here, this study aimed to assess the potential role of the miR-15a-5p/cell division cycle-related protein 4 (CDCA4) axis in breast cancer (BC) resistance to Adriamycin. METHODS: In the present study, the relative expression of miRNA-15a-5p in MCF-7/ADR, MCF-7 and Hs578Bst was measured by qRT-PCR. MCF-7/ADR cells underwent transfection with an miR-15a-5p mimic and inhibitor, respectively. Transwell assays, flow cytometry and CCK8 were performed to examine the potential effects of the abnormal expression of miR-15a-5p. The association of aberrant miR-15a-5p expression with Adriamycin resistance in BC was determined in cultured MCF-7/ADR cells. Bioinformatics was employed to predict the genes targeted by miR-15a-5p. Moreover, the correlation between miR-15a-5p and its target gene, CDCA4, was evaluated based on qRT-PCR data. RESULTS: The expression of miR-15a-5p was significantly downregulated in MCF/ADR cells compared with MCF-7 and Hs578Bst cell lines. In the presence of Adriamycin, miR-15a-5p overexpression significantly increased cell chemosensitivity, as well as MCF-7/ADR cell proliferation, invasion, and migration, while promoting apoptosis and inducing cell-cycle arrest in the synthesis phase. CDCA4 RNA interference enhanced these effects as shown in our previous study. Bioinformatics identified CDCA4 as an miR-15a-5p target gene. qRT-PCR further demonstrated that CDCA4 and miR-15a-5p expression levels were inversely correlated. CONCLUSION: Adriamycin resistance in BC cells was, at least in part, altered by mRNA-15a-5p via regulation of its target gene, CDCA4, by controlling the cell cycle, which may provide some novel ideas for BC chemotherapy in the future.

Risk Score Based on Two microRNAs as a Prognostic Marker of Hepatocellular Carcinoma and the Corresponding Competitive Endogenous RNA Network.

PURPOSE: Liver transplantation (LT) currently yields the best outcomes for hepatocellular carcinoma (HCC). However, tumor recurrence still occurs in some patients. Identifying markers that predict HCC recurrence after LT is an unmet medical need. METHODS: In this study, differential expression analysis was used to identify differentially expressed microRNAs (DEmiRs) between HCC and liver tissues in the The Cancer Genome Atlas database and in data from patients with recurrent or non-recurrent HCC in the GSE64989 dataset. The expression profiles of the overlap DEmiRs were used to construct an miRNA-based risk score to predict prognosis using Cox regression analysis. The target genes of the miRNAs of interest were predicted, and they were analyzed for functional enrichment. Furthermore, we used the miRNAs of interest to construct a competitive endogenous RNA (ceRNA) network of long non-coding RNAs (lncRNAs), miRs and mRNAs. RESULTS: Four up-regulated and three down-regulated miRNAs in HCC and recurrent HCC after LT were considered as candidate miRs. MiR-3200-3p and miR-3690 were selected to construct the miR-based risk score, which was found to be associated with poor overall survival and progression-free survival. Furthermore, it proved to be an independent prognostic factor after adjusting for other clinicopathological factors. The corresponding ceRNA networks of these two miRs that we constructed may help to understand their regulatory mechanisms in HCC. CONCLUSION: We propose a risk score based on miR-3200-3p and miR-3690 that may be useful as a prognostic marker to predict HCC recurrence after LT. We generated a ceRNA network involving these miRNAs, which may help reveal their regulatory roles in HCC.

Knockdown of cell division cycle-associated protein 4 expression inhibits proliferation of triple negative breast cancer MDA-MB-231 cells in vitro and in vivo.

Cell division cycle-associated protein 4 (CDCA4), also known as SEI-3/hematopoietic progenitor protein, is a target gene of transcription factor E2F and represses E2F-dependent transcriptional activation and cell proliferation. The present study investigated the effects of CDCA4 knockdown on the regulation of triple negative breast cancer (TNBC) cell proliferation in vitro and in vivo. Human TNBC MDA-MB-231 cells were subjected to CDCA4 expression knockdown using a lentiviral vector carrying CDCA4 or a negative control short hairpin RNA, and reverse transcription-quantitative polymerase chain reaction, MTT cell viability, cell growth, flow cytometric apoptosis, cell cycle and nude mouse tumorigenesis assays were conducted. The knockdown of CDCA4 expression effectively inhibited the growth of MDA-MB-231 cells by promoting apoptosis in vitro. Additionally, CDCA4 expression knockdown suppressed nude mouse tumor cell xenograft formation and growth in vivo. In conclusion, the data from the present study supported the hypothesis that CDCA4 may be involved in regulating human TNBC progression, and that targeting CDCA4 expression could be useful as a novel strategy in future TNBC treatment.

CDCA4, a downstream gene of the Nrf2 signaling pathway, regulates cell proliferation and apoptosis in the MCF­7/ADM human breast cancer cell line.

The present study aimed to examine the effect of RNA interference targeting cell division cycle­associated protein 4 (CDCA4) on the proliferation and apoptosis of the MCF­7/ADR' human breast cancer cell line. CDCA4 has been shown to have a unique role in regulating cell cycle. In the present study, the expression of CDCA4 was suppressed by CDCA4­specific short hairpin (sh)RNA transfection of the human breast cancer cells, following which changes in the proliferation and apoptosis of the CDCA4­knockdown cells were compared with those of control shRNA­transfected cells. The results confirmed that CDCA4 RNA interference reduced the percentage of human breast cancer cells to <50%. In addition, RNA interference of CDCA4 resulted in a significant increase in the apoptotic rate of cells. Taken together, these results suggested that CDCA4 enhanced proliferation and reduced apoptosis in the MCF­7/ADM human breast cancer cells in vitro.