MiR-363 restrain the proliferation, migration and invasion of colorectal carcinoma cell by targeting E2F3.

MicroRNA (miRNA) is associated with tumor cell proliferation, migration and invasion. Studies have shown that miRNAs are closely related to the occurrence and development of colorectal cancer (CRC), but the mechanisms deserve further investigation. In this study, we aim to explore the role of miR-363 on CRC tumorigenesis. Using CRC cell lines, we tested the expression of miR-363 by using RT-PCR, and miR-363 effect on cell behavior was test by using CCK-8 assay, wound-healing assay and cell invasion assay, and western blotting. Luciferase reporter assay and western blot confirmed that E2F3 was the target gene for miR-363. We further examined the effect of E2F3 on the regulation of miR-363 on cell behavior through knockdown of E2F3. Western blot and RT-PCR assay showed that miR-363 inhibited the expression of E2F3 in HCT-116 and SW480 cell. MiR-363 overexpression or E2F3 knockdown inhibited cell proliferation, migration and invasion of CRC. This study demonstrated that miR-363 is able to suppress cell proliferation, migration and invasion by negative regulating E2F3 in CRC cells, and inhibits tumor growth in vivo.

Corrigendum: STAT5a Confers Doxorubicin Resistance to Breast Cancer by Regulating ABCB1.

[This corrects the article DOI: 10.3389/fonc.2021.697950.].

CRNDE silencing promotes apoptosis and enhances cisplatin sensitivity of colorectal carcinoma cells by inhibiting the Akt/mTORC1-mediated Warburg effect.

Colorectal cancer (CRC) is one of the most prevalent gastrointestinal tumors worldwide, with a high mortality rate. The lncRNA colorectal neoplasia differentially expressed (CRNDE) is upregulated in CRC and is involved in regulating the apoptosis, proliferation, and drug sensitivity of CRC cells. However, the specific underlying mechanisms remain to be elucidated. The aim of the present study was to investigate the effects of CRNDE on the Warburg effect in CRC cells, as well as the associated mechanisms. The expression of CRNDE in HCT-116 cells was overexpressed or silenced by transfection. Apoptosis, cisplatin sensitivity, the Warburg effect, and Akt/mTOR activation were evaluated. The results demonstrated that CRNDE inhibition decreased the proliferation and increased the apoptosis and cisplatin sensitivity of HCT-116 cells. In addition, CRNDE inhibition attenuated the Warburg effect in HCT-116 cells, as verified by a decrease in ATP production, lactic acid levels, glucose uptake, and the expression of Warburg effect-related enzymes (GLUT1, LDHA, HK2, and PKM2). CRNDE inhibition also suppressed the activity of the Akt/mTORC1 pathway, as demonstrated by the decreased phosphorylation of Akt, S6K, S6, and mTOR and the increased phosphorylation of 4EBP-1 and EIF-4E. The CRNDE overexpression-induced increase in ATP and lactic acid levels and glucose uptake in HCT-116 cells was reversed by Akt and mTOR inhibitors. These findings indicate that CRNDE silencing promotes apoptosis and enhances cisplatin sensitivity in colorectal carcinoma cells, which may be mediated by the regulation of the Warburg effect via the Akt/mTORC1 pathway. The present study thus provides a potential strategy for the treatment of CRC.

Tianwang Buxin Granules Influence the Intestinal Flora in Perimenopausal Insomnia.

METHODS: The subjects included 13 PI patients from the Hubei Provincial Hospital of TCM, Hubei University of TCM, and Wuhan Traditional Chinese Medicine Hospital, and the corresponding noninsomniac spouses of the patients were selected as controls. TWBXG was continuously administered for 4 weeks. The feces of PI patients and their noninsomniac spouses before and after treatment with TWBXG were collected. The intestinal flora composition of each group was detected by metagenomic sequencing, and the efficacy of TWBXG was evaluated by the PSQI scale. RESULTS: Compared with the control group, the model group showed an increase in the abundance of Roseburia faecis, Ruminococcus, Prevotella copri, Fusicatenibacter saccharivorans, and Blautia obeum, while those of Bacteroides, fecal Bacteroidetes, and Faecalibacterium prausnitzii were decreased. Compared with pretreatment, the PSQI score was significantly reduced (P < 0.05), the abundance of Bacteroides, fecal Bacteroidetes, and Faecalibacterium prausnitzii increased, and that of Roseburia faecis, Ruminococcus, Prevotella copri, Fusicatenibacter saccharivorans, and Blautia obeum decreased after treatment. However, there was still a certain gap in the abundance of related flora in the treatment group compared with the control. CONCLUSION: PI is associated with disturbances in the intestinal flora and is mainly related to the disorders of Roseburia faecis, Ruminococcus, Prevotella copri, Fusicatenibacter saccharivorans, Blautia obeum, Bacteroides, fecal Bacteroidetes, and Faecalibacterium prausnitzii. TWBXG can effectively treat PI, and its effect may be achieved by regulating the disordered intestinal flora. Clinical Trials. The study was registered in the Chinese clinical trial registry and approved by the World Health Organization clinical trial registration platform (Effects of the modified Tianwang Buxin granule and modified Tianwang Buxin decoction pieces on insomnia: a randomized, controlled trial, ChiCTR-IPR-17011549).

STAT5a Confers Doxorubicin Resistance to Breast Cancer by Regulating ABCB1.

Chemoresistance is a daunting challenge to the prognosis of patients with breast cancer. Signal transducer and activator of transcription (STAT) 5a plays vital roles in the development of various cancers, but its function in breast cancer is controversial, and its role in chemoresistance in breast cancer remains unexplored. Here we identified STAT5a as a chemoresistance inducer that regulates the expression of ABCB1 in breast cancer and can be targeted by pimozide, an FDA-approved psychotropic drug. First, we found that STAT5a and ABCB1 were expressed at higher levels in doxorubicin-resistant cell lines and chemoresistant patients, and their expression was positively correlated. Then, we confirmed the essential roles of STAT5a and ABCB1 in doxorubicin resistance in breast cancer cells and the regulation of ABCB1 transcription by STAT5a. Subsequently, the efficacy of pimozide in inhibiting STAT5a and sensitizing doxorubicin-resistant breast cancer cells was tested. Finally, we verified the role of STAT5a in doxorubicin resistance in breast cancer and the efficacy of pimozide in reversing this resistance in vivo. Our study demonstrated the vital role of STAT5a in doxorubicin resistance in breast cancer. Targeting STAT5a might be a promising strategy for treating doxorubicin-resistant breast cancer. Moreover, repurposing pimozide for doxorubicin resensitization is attractive due to the safety profile of pimozide.

Tian Wang Bu Xin Dan for Insomnia: A Systematic Review of Efficacy and Safety.

BACKGROUND: The Traditional Chinese Medicine (TCM) Tian Wang Bu Xin Dan (TWBXD) has been used widely for treating insomnia in China. The purpose of this meta-analysis was to evaluate the efficacy and safety of TWBXD in the treatment of insomnia. OBJECTIVE: This study evaluated the efficacy and safety of TWBXD for insomnia. METHODS: We searched seven main databases including PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Chinese Biomedicine Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), and Wan-fang. We identified randomized-controlled trials (RCTs) for insomnia treatment involving TWBXD, TWBXD combined with conventional Western medicine, and conventional Western medicine from their inception to May 2018. The quality of literature was evaluated by Cochrane assessing tool to reduce the risk of bias. Meta-analysis and heterogeneity of results across the trials were performed. RevMan 5.3 was used to synthesize the results. RESULTS: 14 studies involving 1,256 participants were identified in this systematic review. Methodological deficiencies existed in most of the included trials. Few studies described the generation of a random sequence in detail, the concealment of allocation, and the methods of blinding. No placebo was used in treatment. 12 trials compared TWBXD with conventional Western medicine and 2 trials compared TWBXD combined with conventional Western medicine. The results of our meta-analysis showed relative benefits in effective rates in favor of TWBXD (Odds Ratio [OR] 2.71, 95% confidence interval [CI] 1.67 to 4.39, P < 0.00001) and TWBXD combined with conventional Western medicine (OR 5.05, 95% CI 1.58 to 16.12, P=0.006). The Pittsburgh Sleep Quality Index (PSQI) scores showed similar results, which favored TWBXD (Weighted Mean Difference [WMD] -1.82, 95% CI -3.00 to -0.64, P=0.003). Only 5 trials reported adverse events, whereas the other 9 trials did not provide the safety information. CONCLUSION: This review demonstrates that although the effects of TWBXD on insomnia were promising, they need to be interpreted with caution, due to the poor methodological quality and the small number of trials of the included studies. TWBXD seems to be generally safe, but there is insufficient evidence to make conclusions on the safety because fewer studies reported the adverse events. Further studies on a larger scale with more rigorous designs are required to evaluate the role of TWBXD in the insomnia treatment.

Efficacy and Safety of the TCM Qi-Supplementing Therapy in Patients with Myasthenia Gravis: A Systematic Review and Meta-Analysis.

BACKGROUND: The Traditional Chinese Medicine (TCM) Qi-supplementing therapy has been used widely for treating myasthenia gravis (MG) in China. The purpose of this meta-analysis was to evaluate the efficacy and safety of Qi-supplementing therapy as an adjunctive therapy in MG patients. METHODS: Seven electronic databases were searched through June 2016. Randomized controlled trials (RCTs) evaluating the add-on effect of Qi-supplementing therapy in MG patients were included. The outcome measures were the total effective rate, relapse rate, and adverse events. RESULTS: Twenty-three RCTs involving 1,691 MG patients were included. The included studies were of low-to-moderate quality. Meta-analysis showed that Qi-supplementing therapy combined with Western medicine (WM) significantly improved the total response rate and reduced the relapse risk during 6-24 months of follow-up. Subgroup analysis showed that Qi-supplementing therapy only affected the total response rate within the first 6 months of treatment. Moreover, the rate of adverse events was lower with the addition of Qi-supplementing therapy to WM than with WM only. CONCLUSIONS: Short-term Qi-supplementing therapy combined with WM appears to be superior to WM for improving the total response rate and reducing the relapse rate. However, more high-quality RCTs are warranted owing to methodological flaws of previous trials.