mTOR signaling-related MicroRNAs and Cancer involvement

Wang, Ping; Liu, Xiaomin; Lei, Ding; Zhang, Xin-Ju

doi:10.7150/jca.22119

Cited by 37 publications

(26 citation statements)

References 117 publications

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“…Currently, the mTORC1 inhibitors, rapamycin as well as its analogues have been approved for the treatment of several types of human cancer, such as renal cell carcinoma, mantle cell lymphoma, and some TSCrelated tumors, including lymphangioleiomyomatosis, angiomyolipomas, and subependymal giant cell astrocytomas [6,[16][17][18]. Numerous studies indicate that mTORC1 signaling pathway is regulated by miRNAs [10]. However, little is known about how miRNAs function in the dysregulated mTORC1mediated tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

“…With respect to carcinogenesis, miRNAs can act as either oncogenes or tumor suppressors, depending on the genes they regulate and the cellular context [9]. Numerous studies have shown that dysregulation of miRNAs plays an essential role in tumorigenesis through modulation of AKT/mTORC1 signaling pathway [10]. However, the function of miRNAs in mTORC1-induced tumorigenesis remains largely unknown.…”

Section: Introductionmentioning

confidence: 99%

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miR-125b-5p/STAT3 Pathway Regulated by mTORC1 Plays a Critical Role in Promoting Cell Proliferation and Tumor Growth

Zhang¹,

Wan²,

Tang³

et al. 2020

J. Cancer

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Aberrant activation of the mammalian target of rapamycin complex 1 (mTORC1) plays a critical role in tumorigenesis. However, the precise underlying mechanism is still not fully understood. Although accumulating evidence suggests that mTORC1 signaling is regulated by microRNAs (miRNAs), whether miRNAs are involved in the tumorigenesis mediated by mTORC1 dysregulation remains largely unclear. In our study, the comparison between tuberous sclerosis complex 1 (Tsc1) -/-or Tsc2-/-mouse embryonic fibroblasts (MEFs) and the control cells revealed the involvement of microRNA-125b-5p (miR-125b-5p) in the tumorigenesis driven by mTORC1 activation. Our study also showed that loss of TSC1 or TSC2 led to significant downregulation of miR-125b-5p and upregulation of signal transducer and activator of transcription 3 (STAT3) via mTORC1 activation. Overexpression of miR-125b-5p inhibited the proliferation of the cells with hyperactivated mTORC1 both in vitro and in vivo. Furthermore, we demonstrated that STAT3 is a direct target of miR-125b-5p. Depletion of STAT3 mimicked the effect of ectopic expression of miR-125b-5p, and reintroduction of STAT3 rescued the compromised cell proliferation driven by miR-125b-5p overexpression in Tsc1-/-or Tsc2-/-MEFs. We conclude that the miR-125b-5p/STAT3 pathway plays a crucial role in hyperactivated mTORC1-mediated tumorigenesis and miR-125b-5p is a potential therapeutic target.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

miR-125b-5p/STAT3 Pathway Regulated by mTORC1 Plays a Critical Role in Promoting Cell Proliferation and Tumor Growth

Zhang¹,

Wan²,

Tang³

et al. 2020

J. Cancer

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“…The mTOR pathway plays as a critical effector in cell signaling pathways that regulates various cellular processes including apoptosis, autophagy, protein synthesis, and energy metabolism . It has been recently demonstrated that there are several miRNAs that oppose mTOR signaling and might have potential therapeutic implications in cancer therapy (summarized in Figure ) …”

Section: Mirnas Are Involved In Mtor Suppression In Cancersmentioning

confidence: 99%

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

Javid

Soltani

Mohammadi

et al. 2019

J of Cellular Biochemistry

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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

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“…Due to its antiproliferative properties, mTOR inhibitors have also been approved as anticancer drugs [ 280 – 282 ]. Intriguingly, the identification of miRNAs as novel emerging regulators of mTOR signaling has provided new insights into a multitude of biological processes, especially in tissue remodeling and hypertrophy, which has been appreciated by the scientific community in cardiac physiology [ 103 , 169 , 185 ]. Hypertrophic stimuli such as phenylephrine [ 283 ], angiotensin II (Ang II) [ 37 , 284 , 285 ], and endothelin-1 [ 286 ] are known to activate mTORC1 in the heart and result in robust vascular remodeling leading to heart failure [ 274 ].…”

Section: Mtor In Cardiovascular Diseasesmentioning

confidence: 99%

Emerging Role of mTOR Signaling‐Related miRNAs in Cardiovascular Diseases

Samidurai

Kukreja

Das

2018

Oxidative Medicine and Cellular Longevity

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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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mTOR signaling-related MicroRNAs and Cancer involvement

Cited by 37 publications

References 117 publications

miR-125b-5p/STAT3 Pathway Regulated by mTORC1 Plays a Critical Role in Promoting Cell Proliferation and Tumor Growth

miR-125b-5p/STAT3 Pathway Regulated by mTORC1 Plays a Critical Role in Promoting Cell Proliferation and Tumor Growth

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

Emerging Role of mTOR Signaling‐Related miRNAs in Cardiovascular Diseases

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