Retraction: Down-regulated LncR-MALAT1 suppressed cell proliferation and migration by inactivating autophagy in bladder cancer.

[This retracts the article DOI: 10.1039/C8RA04876B.].

MicroRNA miR-124-3p suppresses proliferation and epithelial-mesenchymal transition of hepatocellular carcinoma via ARRDC1 (arrestin domain containing 1).

Hepatocellular carcinoma (HCC) is responsible for high morbidity and mortality worldwide. Increasing evidence suggests that microRNAs intensively participate in HCC development and progression. In the current study, we aimed to explore the impact of miR-124-3p in the proliferation and epithelial-mesenchymal transition (EMT) of HCC. The RT-qPCR assay was employed to determine miR-124-3p expression in human HCC specimens and cell lines. Luciferase assay was used to validate the miR-124-3p target gene. Western Blot and RT-qPCR were performed to study the effects of miR-124-3p modulation on ARRDC1 (Arrestin Domain Containing 1) mRNA and protein expressions. MTT assay, wound healing assay, EdU assay, and Transwell assay were utilized to verify the impact of miR-144-3p modulation on HCC proliferation and EMT via ARRDC1. We found that MiR-124-3p expression downregulates in HCC. Overexpression of miR-124-3p reduced the HCC cell proliferation and EMT. Meanwhile, we determined that the expression of ARRDC1 is increased in HCC, and miR-124-3p directly binds the 3'UTR of ARRDC1 and inhibits its expression at mRNA and protein level, suggesting that miR-124-3p was capable of negatively modulating ARRDC1. Besides, cotransfection of ARRDC1-overexpression plasmid and miR-124-3p mimics increased the cell proliferation and EMT as compared to miR-124-3p mimics. Our study concluded that miR-124-3p directly binds the 3'UTR of ARRDC1 and exerts anti-tumorous effects by inhibiting the HCC proliferation and EMT. Therefore, miR-124-3p/ARRDC1 axis may serve as a novel therapeutic target to inhibit HCC growth and metastasis.

Preoperative neoadjuvant chemotherapy combined with radical surgery in cervical cancer.

PURPOSE: To investigate the efficacy of preoperative neoadjuvant chemotherapy combined with radical surgery on cervical cancer patients and its effect on the prognosis of patients and serum squamous cell carcinoma antigen (SCC-Ag) level. METHODS: 163 patients with cervical cancer composed the research group. Among them, 72 patients treated with radical resection of cervical cancer were enrolled in the control group, while the remaining 91 patients were enrolled in the study group and treated with preoperative neoadjuvant chemotherapy combined with radical resection of cervical cancer. The clinical indicators during and after the surgery, as well as the efficacy, were compared between the two groups. Serum SCC-Ag level before and after the treatment was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The total effective rate of the study group was statistically higher than that of the control group (p<0.05). Seven cases (9.72%) of adverse reactions occurred in the control group. Thirteen cases (12.09%) of adverse reactions occurred in the study group. The serum SCC-Ag levels of the two groups after the treatment were significantly lower than those before the treatment, with a sharper decrease in the study group (p<0.05). CONCLUSION: Preoperative neoadjuvant chemotherapy combined with radical surgery has remarkable efficacy in cervical cancer patients, and can significantly reduce serum SCC-Ag levels in patients, which is worthy of clinical promotion.

miR-21 promotes cell migration and invasion of hepatocellular carcinoma by targeting KLF5.

Previous studies have reported that microRNAs regulate gene expression and transcription. miR-21 have been identified to play a role in many types of cancer. KLF5 functions as a tumor inhibitor in certain cancers. However, the role of KLF5 plays in hepatocellular carcinoma (HCC), especially concerning the relationship between miR-21 and the KLF5 gene remains to be determined. Reverse transcription-quantitative PCR (RT-qPCR), western blot analysis, as well as luciferase reporter and Transwell assays were used to determine the expression of miR-21 and KLF5 in Huh 7, SK-HEP-1, LO-2, and HCC tissues. In HCC cells and tissues, the upregulation of miR-21 was identified. HCC cell migratory and invasive abilities significantly increased because of miR-21 overexpression. KLF5 expression was inhibited by miR-21 by targeting its 3'-UTR. KLF5 overexpression alleviated the effect induced by miR-21 on the migratory and invasive ability of the Huh 7 cells. The results therefore show that, HCC cell migration and invasion is significantly suppressed by miR-21 via targeting KLF5. The newly identified miR-21/KLF5 axis provides a useful therapeutic biomarker for HCC treatment.

Down-regulated LncR-MALAT1 suppressed cell proliferation and migration by inactivating autophagy in bladder cancer.

Long non-coding RNA-metastasis-associated lung adenocarcinoma transcript (LncR-MALAT) is highly expressed in a variety of tumors, which can affect the progression of tumor cells. LncR-MALAT1 was reported to affect the proliferation of pancreatic cancer and glioma cells by regulating autophagy, but how LncR-MALAT1 affects the proliferation and invasion of various cancer cells by regulating autophagy in bladder cancer has not been reported. Therefore, in this study, we aimed to investigate the effect of LncR-MALAT1 on cell proliferation, apoptosis, invasion and autophagy of bladder cancer and the possible mechanism in vitro. The results showed that LncR-MALAT1 was highly expressed in bladder cancer tissues and cells. The silence of LncR-MALAT1 inhibited the proliferation and invasion and promoted apoptosis in bladder cancer cells. In addition, MALAT1 shRNA down-regulated the expression of Beclin1 and the LC3 II/I ratio, enhanced the expression of p62 and played a significant role in autophagy inhibition. By further investigating the relevant regulatory mechanisms, we found that MALATI shRNA reduced the phosphorylation of AMPK and increased the phosphorylation level of mTOR, thereby inhibiting the activation of the AMPK/mTOR pathway. It is noteworthy that the AMPK/mTOR pathway activator, metformin, partially reversed the effect of MALAT1 shRNA on the inhibition of autophagy in bladder cancer cells. At the same time, the proliferation and invasion ability of HT-1376 cells inhibited by MALAT1 shRNA were also enhanced. The results showed that down-regulation of LncR-MALAT1 could inhibit the proliferation and invasion of bladder cancer cells by attenuating autophagy via the regulation of the AMPK/mTOR pathway.

Acidity-promoted cellular uptake and drug release mediated by amine-functionalized block polycarbonates prepared via one-shot ring-opening copolymerization.

This paper reports a drug nanovehicle self-assembled from an amine-functionalized block copolymer poly(6,14-dimethyl-1,3,9,11-tetraoxa-6,14-diaza-cyclohexadecane-2,10-dione)-block-poly(1,3-dioxepan-2-one) (PADMC-b-PTeMC), which is prepared by controlable ring-opening block copolymerization attractively in a "one-shot feeding" pathway. The copolymers display high cell-biocompatibility with no apparent cytotoxicities detected in 293T and HeLa cells. Due to their amphiphilic nature, PADMC-b-PTeMC copolymers can self-assemble into nanosized micelles capable of loading anticancer drugs such as camptothecin (CPT) and doxorubicin (DOX). In particular, the outer PADMC shell endows the PADMC-b-PTeMC nanomicelles with pH-dependent control over the micellar morphology, cell uptake efficiency, and the drug release pattern. Confocal inspection reveals the remarkably enhanced cellular internalization of drug loaded micelles by cancerous HeLa cells at relatively lower pH 5.8 simulating the mildly acid microenvironment in tumors. Along with the acidity-triggered volume expansion of micelles, an accelerated CPT release in vitro occurs. The obtained results adumbrate the possibility of completely biodegradable PADMC-b-PTeMC as pH-sensitive drug carriers for tumor chemotherapy.

Triple-stimuli (pH/thermo/reduction) sensitive copolymers for intracellular drug delivery.

The development of novel thermo-, pH- and reduction-sensitive polymeric micelles based on a block copolymer p(PEG-MEMA-co-Boc-Cyst-MMAm-co-VI)-b-PEG (PPBV) for the intracellular delivery of anticancer drugs is reported. The pH/temperature-responsive behaviour of PPBV is observed by both DLS and UV-Vis experiments. The PPBV micelles prepared by a quick heating process are stable in PBS (pH 7.4, 37 °C) for over 48 h and are stable in the presence of serum for at least 12 h. Paclitaxel (PTX) was loaded into the PPBV micelles with a high encapsulation efficiency (>85%), resulting in a high drug loading content (up to 26 wt%) by a simple heating method. The PTX-loaded micelles show slow drug release in PBS and rapid release after exposure to a weakly acidic pH or reductive environment. The PTX-loaded micelles showed higher cytotoxicity against HepG2 cells with increasing PTX concentration, whereas empty micelles are found to be non-toxic. These multi-sensitive polymeric micelles may serve as promising carriers for cytostatic drugs.