MicroRNA-126-5p Inhibits the Migration of Breast Cancer Cells by Directly Targeting CNOT7.

BACKGROUND: To assess the effect of microRNA-126-5p (miR-126-5p) on the migration of the breast cancer MCF7 cell line. METHODS: GSE143564 was downloaded from the Gene Expression Omnibus (GEO; http://www.ncbi.nlm.nih.gov/geo) to identify the differentially expressed miRNAs between breast cancer and adjacent tissues. Quantitative reverse transcription PCR (RT-qPCR) was used to assess miR-126-5p levels in the normal 184A1 breast cell line and the breast cancer MCF7 cell line. The MCF7 cell line was then transfected with miR-126-5p mimics or corresponding negative control (NC-mimic). The proliferation and migration abilities of the MCF7 cell line were measured by methyl thiazolyl tetrazolium (MTT), Transwell and scratch healing assays. CCR4-NOT transcription complex and subunit 7 (CNOT7) expression levels in the NC-mimic and miR-126-5p mimic groups were measured by Western blot analysis. Bioinformatic analysis and a dual-luciferase reporter assay were performed to identify the miR-126-5p target gene. RESULTS: One hundred forty-eight differentially expressed miRNAs (downregulated = 55, upregulated = 93) were identified. MiR-126-5p expression in the MCF7 cell line was significantly downregulated relative to that of 184A1 cell line (P < 0.05). Compared with that observed in the control and NC-mimic groups, cell proliferation in the miR-126-5p mimic group was significantly decreased at 48 and 72 h posttransfection (P < 0.05). In addition, the scratch healing rate and number of membrane-piercing cells in the miR-126-5p overexpression group were lower than those detected in the control and NC groups (P < 0.05). Furthermore, miR-126-5p could reduce the luciferase activity for the wild-type CNOT7 gene 3'-untranslated region (UTR) reporter (P < 0.05) but had no effect on the mutant 3'UTR reporter (P > 0.05). Compared with that observed in the NC and control groups, the levels of CNOT7 in the miR-126-5p overexpression group decreased (P < 0.05). CONCLUSION: Upregulation of miR-126-5p can inhibit the migration of the breast cancer MCF7 cell line, which may involve its direct targeting of the 3'UTR of CNOT7.

PEG/PEI-functionalized single-walled carbon nanotubes as delivery carriers for doxorubicin: synthesis, characterization, and in vitro evaluation.

Single-walled carbon nanotubes (SWCNTs) have attracted great interest regarding drug-delivery applications. However, their application has been limited by some inherent disadvantages. In this study, raw SWCNTs were purified with different oxidizing acids, and the resulting shortened CNTs were conjugated with poly(ethylene glycol) (PEG) and polyethylenimine (PEI). The different nanocarriers, that is, CNTs-COOH (CNTs), CNTs-PEG and CNTs-PEG-PEI, were systematically characterized and evaluated in terms of drug loading, in vitro release, cytotoxicity towards MCF-7 cells and cellular uptake. The results showed that all CNT carriers had a high drug loading capacity. In comparison with CNTs-COOH and CNTs-PEG, CNTs-PEG-PEI showed a more rapid drug release under acidic conditions and a higher antitumor activity. Furthermore, fluorescence detection and flow cytometry (FCM) analysis results indicated that the internalization into cells of CNTs-PEG-PEI was significantly enhanced, thus inducing tumor cell death through apoptosis more efficiently. The above series of benefits of CNTs-PEG-PEI may be attributed to their good dispersibility and comparably higher affinity to tumor cells due to the difunctionalization. In summary, the PEG- and PEI-conjugated CNTs may be used as novel nanocarriers and the findings will contribute to the rational design of multifunctional delivery vehicles for anticancer drugs.

The Effects of Salvianolate Combined With Western Medicine on Diabetic Nephropathy: A Systematic Review and Meta-Analysis.

BACKGROUND: Salvianolate, a compound mainly composed of salvia magnesium acetate, is extracted from the Chinese herb Salvia miltiorrhiza. Because of its biological activity, easy quality control and certain efficacy, salvianolate is widely used in treating ischemic cardiocerebral vascular disease, liver damage, renal injury, diabetes, and its complications. Particularly, it has potential protective effects on diabetic nephropathy (DN). OBJECTIVE: This meta-analysis aimed to evaluate the efficacy and safety of salvianolate when combined with western medicine in patients affected with DN. METHODS: We searched Pubmed, Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Data knowledge service platform (Wanfang Data), Chinese Scientific Journal Database (VIP), and China Biology Medicine Disc (SinoMed) for randomized controlled trials (RCTs) of salvianolate in combination with western medicine on DN, including results from the foundation of each database until November 30, 2019. Two reviewers independently performed literature screening, data extraction, and quality evaluation. This meta-analysis was carried out using RevMan5.3 software. RESULTS: From the 12 RCTs, 1,030 patients from China were involved. Compared with single-use western medicine, the combination of salvianolate and western medicine for the treatment of DN could reduce levels of serum creatinine (Scr) [MD=-16.53, 95% CI (-28.79, -4.27), P=0.008], blood urea nitrogen (BUN) [MD=-1.40, 95% CI (-2.17, -0.62), P=0.0004], urinary albumin excretion rate (UARE) [SMD=-1.84, 95% CI (-2.70, -0.98), P < 0.0001], 24-hour urinary protein (24h Upro) [MD=-0.37, 95% CI (-0.47, -0.26), P < 0.00001], albumin-to-creatinine ratio (ACR) [SMD=-1.43, 95% CI (-2.64, -0.23), P=0.02], hypersensitive C-reactive protein (hs-CRP) [MD=-5.69, 95% CI (-7.09, -4.29), P < 0.00001], interleukin-6 (IL-6) [MD=-12.53, 95% CI (-18.55, -6.52), P < 0.0001], malondialdehyde (MDA) [SMD=-2.05, 95% CI (-3.67, -0.43), P=0.01], as well as improve clinical efficacy [RR=1.21, 95% CI (1.12,1.31), P < 0.00001], and increase superoxide dismutase (SOD) levels [SMD=1.12, 95% CI (0.86,1.38), P < 0.00001]. No increase in the occurrence of serious adverse events were observed in the treatment group compared with the control group. CONCLUSION: This study indicated that salvianolate combined with western medicine contributes to protecting renal function, inhibiting inflammation, and exhibiting anti-oxidative properties, thereby improving clinical efficacy. Thus, salvianolate can be considered as a potential complementary therapy for DN patients. However, due to the low quality of methodology and small sample sizes, more rigorous and larger trials are essential to validate our results.