Emerging roles of microRNAs in regulating the mTOR signaling pathway during tumorigenesis

Abstract

The mammalian target of rapamycin (mTOR) is a large Ser/Thr protein kinase that belongs to the phosphoinositide 3-kinase (PI3K) family and mediates various physiological and pathological processes, especially cell proliferation, protein synthesis, autophagy, and cancer development. The mTOR expression is transient and tightly regulated in normal cells, but it is overactivated in cancer cells. Recently, several studies have indicated that microRNAs (miRNAs) play a critical role in the regulation of mTOR and mTOR-associated processes, some acting as inhibitors and the others as activators. Although it is still in infancy, the strategy of combining both miRNAs and mTOR inhibitors might provide an approach to selectively sensitizing tumor cells to chemotherapy-induced DNA damage and subsequently attenuating the tumor cell growth and apoptosis. K E Y W O R D Sautophagy, cancer, mammalian target of rapamycin, microRNAs, phosphoinositide 3-kinase

Role of tumor microenvironment in the regulation of PD‐L1: A novel role in resistance to cancer immunotherapy

“…The level of PD‐L1 in cancer cells is not only influenced by cytokines, oncogenic transcription factors and some oncogenic activation of the signaling pathways, but also by several signaling patterns of intracellular cells, such as noncoding RNAs (Gong et al, 2014). MicroRNAs (miRs), small noncoding RNAs with 20–22 nucleotides, have been implicated in biological processes including proliferation, apoptosis, and differentiation (Ambros, 2004; Ebrahimi & Hashemy, 2019; Javid, Soltani, Mohammadi, & Hashemy, 2019). Mature miRs can regulate target gene mRNA by binding 3′‐untranslated regions (3′‐UTRs), resulting in degradation or transnational modification of target mRNAs (Fabian & Sonenberg, 2012; Finnegan & Matzke, 2003; Pichler & Calin, 2015).…”

Quercetin: A promising phytochemical for the treatment of glioblastoma multiforme

“…Activated Akt is involved in the downstream mTOR mediated response to the biogenesis of protein and ribosome. In the PI3K pathway, mTOR (mTORC1 and mTORC2) acts as both an upstream regulator and a downstream effector . The activated Akt initiates the mTORC1‐mediated signaling pathway involved in the phosphorylation of eukaryotic initiation factor binding protein 1 (4EBP1), ribosomal protein S6 kinase (pS6k), and eukaryotic initiation factor 4E (eIF4E), which participate in cell growth and proliferation.…”

“…The PI3K/Akt/mTOR signaling network regulates many cellular functions, including cell growth, motility, proliferation, apoptosis, invasion, angiogenesis, metastasis, vesicular trafficking, and survival. [40][41][42] Aberrant PI3K enhances Akt activity and contributes to the majority of characteristics of GBM, including enhanced cell cycle, growth, survival, and motility. Activated Akt is involved in the downstream mTOR mediated response to the biogenesis of protein and ribosome.…”

“…In the PI3K pathway, mTOR (mTORC1 and mTORC2) acts as both an upstream regulator and a downstream effector. 42,43 The activated Akt initiates the mTORC1-mediated signaling pathway involved in the phosphorylation of eukaryotic initiation factor binding protein 1 (4EBP1), ribosomal protein S6 kinase (pS6k), and eukaryotic initiation factor 4E (eIF4E), which participate in cell growth and proliferation. Many studies have proven that the inhibition of the PI3K/Akt/mTOR pathway leads to the release of cytochrome C, activation of caspase-3/-7 and consequently, induction of apoptosis.…”

“…The amplification of EGFR causes the activation of various downstream signaling pathways such as the PI3K/Akt/mTOR pathway. The PI3K/Akt/mTOR signaling network regulates many cellular functions, including cell growth, motility, proliferation, apoptosis, invasion, angiogenesis, metastasis, vesicular trafficking, and survival . Aberrant PI3K enhances Akt activity and contributes to the majority of characteristics of GBM, including enhanced cell cycle, growth, survival, and motility.…”