MicroRNA-18a promotes cancer progression through SMG1 suppression and mTOR pathway activation in nasopharyngeal carcinoma

Shi, Juan; Xiao, Ruo Wen; Shi, Lu; Zhou, Xiao Min; Yang, Tian‐xiao; Zhang, Mei Yin; Weng, Nuo Qing; Zhao, Xin; Wang, Rui Qi; Liu, Ji; Sun, Rui; Qin, Hai; Wang, Hui Yun

doi:10.1038/s41419-019-2060-9

Cited by 40 publications

(41 citation statements)

References 40 publications

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“…Besides that, miR-17-92 cluster members including miR-18a are documented to be overexpressed in NPC tissues [25]. Furthermore, upregulated miR-18a is reported to demonstrate in NPC tissues which is connected with tumor node metastasis stage and tumor size [4]. Experimentally, except for the downregulated TGFBR3 in tongue squamous cell carcinoma [26], there has been another study depicting reduced TGFBR3 in clear-cell renal cell carcinomas accompanied by unwanted prognosis [27].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, it is noticed that overexpressed miR-18a in NPC is believed to connect with NPC metastasis and repressed miR-18a partially contributes to better prognosis of NPC patients [31]. Lately, it is surveyed that downregulation of miR-18a is capable of discouraging NPC proliferation, invasion, and migration [4]. Additionally, a decrease in TGFBR3 expression is regarded to link with laryngeal squamous cell carcinoma (LSCC) invasion and miR-223/TGFBR3 axis regulation takes part in LSCC progression inhibition [32].…”

Section: Discussionmentioning

confidence: 99%

“…Dysregulated microRNAs (miRNAs) are documented to be involved in NPC tumorigenesis, metastasis, invasion, and resistance to radiotherapy and chemotherapy [1]. As a subfamily of miRNAs, miR-18a is found to facilitate NPC progression through suppressor of morphogenesis in genitalia 1 inhibition and mTOR pathway activation [4]. Besides that, miR-18a is further verified to activate NPC cell proliferation and metastasis via DICER1 regulation [5].…”

Section: Introductionmentioning

confidence: 99%

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microRNA-18a from M2 Macrophages Inhibits TGFBR3 to Promote Nasopharyngeal Carcinoma Progression and Tumor Growth via TGF-β Signaling Pathway

Peng

Liu

et al. 2020

Nanoscale Res Lett

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Objectives Nasopharyngeal carcinoma (NPC) is a type of nasopharyngeal disease with high metastasis and invasion properties. Tumor-associated alternative activated (M2) macrophages are evidenced to connect with NPC. Based on this, this study purposes to explore the mechanism and participation of microRNA-18a (miR-18a) from M2 macrophages in NPC. Methods Peripheral blood mononuclear cells were differentiated to macrophages and macrophages were polarized to M2 type by interleukin-4. SUNE-1 and CNE2 cells were transfected with restored or depleted miR-18a or transforming growth factor-beta III receptor (TGFBR3) to explore their roles in NPC progression with the involvement of the TGF-β signaling pathway. Next, SUNE-1 and CNE2 cells were co-cultured with M2 macrophages that had been treated with restored or depleted miR-18a or TGFBR3 to comprehend their combined roles in NPC with the involvement of the TGF-β signaling pathway. Results MiR-18a was highly expressed and TGFBR3 was lowly expressed in NPC cells. MiR-18a restoration, TGFBR3 knockdown or co-culture with miR-18a mimics, or si-TGFBR3-transfected M2 macrophages promoted SUNE-1 cell progression, tumor growth in mice, decreased p-Smad1/t-Smad1, and elevated p-Smad3/t-Smad3. miR-18a downregulation, TGFBR3 overexpression, or co-culture with miR-18a inhibitors or OE-TGFBR3-transfected M2 macrophages depressed CNE2 cell progression, tumor growth in mice, increased p-Smad1/t-Smad1, and decreased p-Smad3/t-Smad3. Conclusion Our study elucidates that miR-18a from M2 macrophages results in promoted NPC cell progression and tumor growth in nude mice via TGFBR3 repression, along with the Smad1 inactivation and Smad3 activation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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microRNA-18a from M2 Macrophages Inhibits TGFBR3 to Promote Nasopharyngeal Carcinoma Progression and Tumor Growth via TGF-β Signaling Pathway

Peng

Liu

et al. 2020

Nanoscale Res Lett

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“…Nuclear factor-kappa B (NF-κB) activation and LMP1 expression can induce miR-18a expression in NPC cells. 95 In summary, in addition to directly targeted inhibition of PI3K, Akt, and mTOR, targeted inhibition of HIF-1α, MK2, CCND1, lncRNA FAM225A, MYH9, MDK, miR-92a, miR-18a, EBV-miR-BART7-3p, FGF2, COL1A1, RBM3, PNUTS, Annexin A1, IL-8, CDKN3, c-Src, Flot-2, EpCAM, OCT4, BEX3, and targeted activation of LZTS2, UBQLN1, SMG1 may become potential therapeutic strategies that affecting the PI3K/Akt pathway in NPC.…”

Section: Crucial Signal Pathways Related To Targeted Therapy Of Npcmentioning

confidence: 99%

Advances in targeted therapy mainly based on signal pathways for nasopharyngeal carcinoma

Kang

Ren

et al. 2020

Sig Transduct Target Ther

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Nasopharyngeal carcinoma (NPC) is a malignant epithelial carcinoma of the head and neck region which mainly distributes in southern China and Southeast Asia and has a crucial association with the Epstein–Barr virus. Based on epidemiological data, both incidence and mortality of NPC have significantly declined in recent decades grounded on the improvement of living standard and medical level in an endemic region, in particular, with the clinical use of individualized chemotherapy and intensity-modulated radiotherapy (IMRT) which profoundly contributes to the cure rate of NPC patients. To tackle the challenges including local recurrence and distant metastasis in the current NPC treatment, we discussed the implication of using targeted therapy against critical molecules in various signal pathways, and how they synergize with chemoradiotherapy in the NPC treatment. Combination treatment including targeted therapy and IMRT or concurrent chemoradiotherapy is presumably to be future options, which may reduce radiation or chemotherapy toxicities and open new avenues for the improvement of the expected functional outcome for patients with advanced NPC.

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“…miRNAs are involved in almost all biological processes, and are major regulators of cell proliferation, apoptosis, differentiation and migration 12,13 . The miRNA miR‐18a is a well‐known oncogenic miRNA, and has been reported to inhibit autophagy in human tumours, such as nasopharyngeal carcinoma 14 . Although the oncogenic role of miR‐18a in the pathological development of cancer and its role in Akt/mTOR pathways has been reported in previous studies, its mechanism in BCC is still not quite clear.…”

Section: Introductionmentioning

confidence: 99%

miR‐18a expression in basal cell carcinoma and regulatory mechanism on autophagy through mTOR pathway

Lai

Liu

et al. 2020

Clin. Exp. Dermatol.

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Summary Background Basal cell carcinoma (BCC) is the most common form of skin carcinoma. Aim To investigate the function of key micro(mi)RNAs and to explore the potential molecular mechanisms involved in BCC. Methods The microarray dataset http://GSE34535, which comprises seven BCC samples and seven control samples, was downloaded from the Gene Expression Omnibus database. Differentially expressed miRNAs (DE‐miRNAs) were identified. We collected tissue samples from 20 patients with BCC and 20 healthy controls (HCs), to compare the miR‐18a expression in their tissue samples. Expression of miR‐18a in A431 and HaCaT cells was also assayed. Following this, we upregulated and downregulated miR‐18a expression in A431 cells to examine the effects on cell proliferation, migration and apoptosis. To further investigate the relative mechanism, the proteins LC3, Beclin 1, Akt and mammalian target of rapamycin (mTOR) were examined by quantitative real‐time PCR and Western blotting. For further verification, we examined the expression of LC3 in the 20 BCC and 20 HC tissue samples. Results In total, 19 DE‐miRNAs (13 upregulated and 6 downregulated) that were common to the BCC and HC groups were identified. Levels of miR‐18a were about three‐fold higher in BCC tissues and A431 cells compared with their respective control groups. In vitro, downregulation of miR‐18a was shown to inhibit cell proliferation and activate autophagy via the Akt/mTOR signalling pathway, while upregulation of miR‐18a promoted proliferation of these cells. LC3 was decreased in BCC compared with HC tissue samples. Conclusions Our data support an oncogenic role of miR‐18a through a novel Akt/mTOR/Beclin 1/LC3 axis, and suggest that the antitumour effects of miR‐18a inhibitor may make it suitable for BCC therapy.

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MicroRNA-18a promotes cancer progression through SMG1 suppression and mTOR pathway activation in nasopharyngeal carcinoma

Cited by 40 publications

References 40 publications

microRNA-18a from M2 Macrophages Inhibits TGFBR3 to Promote Nasopharyngeal Carcinoma Progression and Tumor Growth via TGF-β Signaling Pathway

microRNA-18a from M2 Macrophages Inhibits TGFBR3 to Promote Nasopharyngeal Carcinoma Progression and Tumor Growth via TGF-β Signaling Pathway

Advances in targeted therapy mainly based on signal pathways for nasopharyngeal carcinoma

miR‐18a expression in basal cell carcinoma and regulatory mechanism on autophagy through mTOR pathway

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