ABSTRACT
Objective:To investigate the clinical significance of MAPT-IT1 in breast cancer and its biological effect in vitro.Methods:The expression of MAPT-IT1 in breast cancer was analyzed by TCGA database. 64 cases of breast cancer and normal adjacent tissues were collected. Human breast cancer MDA-MB-231 and MCF-7 cells were cultured and overexpressed MAPT-IT1 or rescue miR-181a-5p by cell transfection. MDA-MB-231 cells were divided into blank group A, overexpression group A and recovery group A; MCF-7 cells were divided into blank group B, overexpression group B and recovery group B. Real time quantitative PCR (RT-qPCR) was used to detect the expression of MAPT-IT1, miR-181a-5p and MAPT mRNA. Western blot was used to detect the expression of MAPT protein. CCK-8 assay was used to detect cell proliferation, and Transwell invasion assay was used to detect cell invasion.Results:The expression of MAPT-IT1 in normal paracancerous tissues and breast cancer tissues was 0.011±0.002 and 0.028±0.003 respectively. The expressions of MAPT-IT1 in breast cancer tissues were significantly higher than those in adjacent normal tissues, and high expression of MAPT-IT1 was correlated with early tumor progression, ER positive and prolonged prognosis ( P<0.05) . In blank group A, overexpression group A and recovery group A, the expressions of MAPT-IT1 were 1.000±0.078, 8.597±0.320 and 8.540±0.177, miR-181a-5p were 1.000±0.027, 0.263±0.024, 4.433±0.239, MAPT were 1.000±0.071, 3.297±0.243, 0.497±0.029. In blank group B, overexpression group B and recovery group B, the expressions of MAPT-IT1 were 1.000± 0.081, 5.716±0.309, 5.288±0.176, miR-181a-5p were 1.000±0.024, 0.291±0.022, 3.648±0.073, and MAPT were 1.000±0.054, 3.309±0.177, 0.883±0.075. After overexpression of MAPT-IT1, the expression of miR-181a-5p was down-regulated, while the expression of MAPT was significantly increased ( P<0.001) , and the proliferation and invasion ability of MDA-MB-231 and MCF-7 cells were significantly decreased ( P<0.05) . Re-expression of miR-181a-5p down-regulated MAPT and promoted cell proliferation and invasion ( P<0.05) . Conclusion:Overexpression of MAPT-IT1 can significantly down-regulate the expression of miR-181a-5p and enhance MAPT and inhibit the malignant phenotype of breast cancer cells in vitro.
ABSTRACT
Alzheimer's disease (AD), the most common neurodegenerative disorder, is characterized by memory loss and cognitive dysfunction. The accumulation of misfolded protein aggregates including amyloid beta (Aβ) peptides and microtubule associated protein tau (MAPT/tau) in neuronal cells are hallmarks of AD. So far, the exact underlying mechanisms for the aetiologies of AD have not been fully understood and the effective treatment for AD is limited. Autophagy is an evolutionarily conserved cellular catabolic process by which damaged cellular organelles and protein aggregates are degraded via lysosomes. Recently, there is accumulating evidence linking the impairment of the autophagy-lysosomal pathway with AD pathogenesis. Interestingly, the enhancement of autophagy to remove protein aggregates has been proposed as a promising therapeutic strategy for AD. Here, we first summarize the recent genetic, pathological and experimental studies regarding the impairment of the autophagy-lysosomal pathway in AD. We then describe the interplay between the autophagy-lysosomal pathway and two pathological proteins, Aβ and MAPT/tau, in AD. Finally, we discuss potential therapeutic strategies and small molecules that target the autophagy-lysosomal pathway for AD treatment both in animal models and in clinical trials. Overall, this article highlights the pivotal functions of the autophagy-lysosomal pathway in AD pathogenesis and potential druggable targets in the autophagy-lysosomal pathway for AD treatment.