Reduced miR-363-3p expression in non-small cell lung cancer is associated with gemcitabine resistance via targeting of CUL4A.

The article "Reduced miR-363-3p expression in non-small cell lung cancer is associated with gemcitabine resistance via targeting of CUL4A", W.-G. Bian, X.-N. Zhou, S. Song, H.-T. Chen, Y. Shen, P. Chen, published in Eur Rev Med Pharmacol Sci 2019; 23 (2): 649-659-DOI: 10.26355/eurrev_201901_16879-PMID: 30720173, has been retracted by the authors due to several inaccuracies in the research design. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/16879.

Inhibition of p53/p21 by TWIST alleviates TNF-α induced nucleus pulposus cell senescence in vitro.

OBJECTIVE: This study aims to reveal the TWIST protein expression in the degenerated nucleus pulposus (NP), its effect on the TNF-α treated NP cells, and to explore its specific mechanism of anti-senescence. PATIENTS AND METHODS: NP tissues from spine fracture patients without intervertebral disc degeneration (IDD) and the IDD patients were collected to detect the TWIST1/2 protein expression by Western blot (WB). NP cells isolated from the healthy tissue was treated with TNF-α to induce senescence, and the TWIST1/2 protein expression was also analyzed. We transfected NP cells with the plasmid coding TWIST to upregulate its expression, which was also cultured in the TNF-α condition. Besides, the TNF-α pretreated NP cells were further stimulated with the recombinant human TWIST1/2 protein. The collagen II and senescent marker ß-galactosidase (ß-gal) were determined by immunofluorescence (IF); the MMP-13, TIMP-3, IL-10, IL-1ß mRNA expression level was detected by quantitative Real Time PCR; the cell proliferation was analyzed by CCK8 assay; the cell cycle was measured by flow cytometry. RESULTS: TWIST1/2 protein was decreased both in the degenerated NP tissue, and TNF-α treated NP cells. The overexpression of TWIST1/2 could prevent the p53, p21, ß-gal, MMP-13, and IL-1ß expression, moreover, it protected the collagen II, TIMP-3, and IL-10 expression in the TNF-α treated NP cells. Additionally, TWIST overexpression also promoted cell proliferation by ensuring the process of the cell cycle. Furthermore, the supplement of TWIST protein was functional to reverse these senescent phenotypes caused by TNF-α partly. CONCLUSIONS: TWIST alleviates the TNF-αinduced NP cells senescence via the inhibition of the p53/p21 pathway.

Reduced miR-363-3p expression in non-small cell lung cancer is associated with gemcitabine resistance via targeting of CUL4A.

OBJECTIVE: Accumulating evidence has suggested that aberrant expression of microRNAs (miRNAs) is associated with non-small cell lung cancer (NSCLC) proliferation, migration, invasion and chemotherapy resistance. Cullin4A (CUL4A) has been previously reported to desensitize NSCLC cells to chemotherapy treatment. However, whether miRNAs regulate CUL4A to promote chemotherapy resistance remains unknown. PATIENTS AND METHODS: Tissues were obtained from 40 NSCLC patients who received surgery at the Yancheng City No. 1 People's Hospital. Cell Counting Kit-8 (CCK-8) assays were applied for the detection of cell proliferation; mRNA and protein levels were determined by Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) and Western blot, respectively. The interaction between mRNA 3'UTR and miRNA was predicted by TargetScan and verified by Dual-Luciferase reporter assay. RESULTS: In the present study, miR-363-3p levels were revealed to be significantly decreased in tumor tissues obtained from NSCLC patients compared with adjacent normal tissues. The results of the CCK-8 assays showed that the overexpression of miR-363-3p may slightly inhibit the proliferation of A549 and H23 cells. Notably, the transfection with miR-363-3p antagonists reduced the sensitivity of A549 and H23 cells to gemcitabine treatment, whereas the overexpression of miR-363-3p markedly increased the sensitivity of A549 and H23 cells to gemcitabine treatment. Furthermore, CUL4A mRNA and protein levels were revealed to be decreased in A549 cells transfected with miR-363-3p mimics. The Dual-Luciferase reporter assay results further suggested that CUL4A represents a target gene of miR-363-3p. CONCLUSIONS: The results indicated that decreased miR-363-3p expression enhanced gemcitabine resistance in NSCLC cells via regulation of CUL4A.