Long noncoding RNA OIP5‐AS1 causes cisplatin resistance in osteosarcoma through inducing the LPAATβ/PI3K/AKT/mTOR signaling pathway by sponging the miR‐340‐5p

Abstract Objective This study aimed to investigate the effect of SIK2 on cisplatin resistance induced by aerobic glycolysis in breast cancer cells and its potential mechanism. Methods qRT-PCR and Western blot were used to detect SIK2 mRNA and protein levels. Cisplatin (DDP) resistant cell lines of breast cancer cells were established, CCK-8 was used to measure and evaluate the viability, and Transwell was used to evaluate the cell invasion capability. Flow cytometry was adopted to evaluate the apoptosis rate. The glycolysis level was evaluated by measuring glucose consumption and lactic acid production. The protein levels of p-PI3K, p- protein kinase B (Akt) and p-mTOR were determined by western blot. Results SIK2 is highly expressed in breast cancer tissues and cells compared with adjacent tissues and normal human breast epithelial cells, and has higher diagnostic value for breast cancer. Silencing SIK2 expression can inhibit proliferation and invasion of breast cancer cells and induce their apoptosis. In addition, SIK2 knockdown inhibits glycolysis, reverses the resistance of drug-resistant cells to cisplatin, and inhibits PI3K/AKT/mTOR signaling pathway. When LY294002 is used to inhibit PI3K/AKT/mTOR signaling pathway, the effect of Sh-SIK2 on aerobic glycolysis of breast cancer cells can be reversed. Conclusion SIK2 can promote cisplatin resistance caused by aerobic glycolysis of breast cancer cells through PI3K/AKT/mTOR signaling pathway, which may be a new target to improve cisplatin resistance of breast cancer cells.

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Emerging Role of mTOR Signaling-Related miRNAs in Cardiovascular Diseases

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/6141902 ◽

2018 ◽

Vol 2018 ◽

pp. 1-23 ◽

Cited By ~ 7

Author(s):

Arun Samidurai ◽

Rakesh C. Kukreja ◽

Anindita Das

Keyword(s):

Cardiovascular Diseases ◽

Cardiovascular System ◽

Signaling Pathway ◽

Noncoding Rna ◽

Current Knowledge ◽

Mammalian Target Of Rapamycin ◽

Vital Role ◽

Mtor Signaling ◽

Cellular Growth ◽

Mtor Signaling Pathway

Mechanistic/mammalian target of rapamycin (mTOR), an atypical serine/threonine kinase of the phosphoinositide 3-kinase- (PI3K-) related kinase family, elicits a vital role in diverse cellular processes, including cellular growth, proliferation, survival, protein synthesis, autophagy, and metabolism. In the cardiovascular system, the mTOR signaling pathway integrates both intracellular and extracellular signals and serves as a central regulator of both physiological and pathological processes. MicroRNAs (miRs), a class of short noncoding RNA, are an emerging intricate posttranscriptional modulator of critical gene expression for the development and maintenance of homeostasis across a wide array of tissues, including the cardiovascular system. Over the last decade, numerous studies have revealed an interplay between miRNAs and the mTOR signaling circuit in the different cardiovascular pathophysiology, like myocardial infarction, hypertrophy, fibrosis, heart failure, arrhythmia, inflammation, and atherosclerosis. In this review, we provide a comprehensive state of the current knowledge regarding the mechanisms of interactions between the mTOR signaling pathway and miRs. We have also highlighted the latest advances on mTOR-targeted therapy in clinical trials and the new perspective therapeutic strategies with mTOR-targeting miRs in cardiovascular diseases.

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