The microRNA miR-33a suppresses IL-6-induced tumor progression by binding Twist in gallbladder cancer

Zhang, Mingdi; Gong, Wei; Zuo, Bin; Chu, Bei; Tang, Zhaohui; Zhang, Yong; Yang, Yong; Zhou, Di; Weng, Mingzhe; Qin, Yiyu; Ma, Mingzhe; Jiang, Alex; Ma, Fei; Quan, Zhiwei

doi:10.18632/oncotarget.12693

Cited by 31 publications

(28 citation statements)

References 39 publications

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“…MiR-33a provides some important functions, such as the regulation of cellular mechanotransduction sensing, mitochondrial biogenesis, and mitochondrial fatty acid oxidation [30,41]. It is known that, in bone tissue, miR-33a plays a role in osteosarcoma chemoresistance by down-regulating TWIST [42] and in osteoblast differentiation after mechanical stimulations [43,44].…”

Section: Discussionmentioning

confidence: 99%

MiR-33a Controls hMSCS Osteoblast Commitment Modulating the Yap/Taz Expression Through EGFR Signaling Regulation

Costa

Carina

Raimondi

et al. 2019

Cells

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Mesenchymal stromal cells (hMSCs) display a pleiotropic function in bone regeneration. The signaling involved in osteoblast commitment is still not completely understood, and that determines the failure of current therapies being used. In our recent studies, we identified two miRNAs as regulators of hMSCs osteoblast differentiation driving hypoxia signaling and cytoskeletal reorganization. Other signalings involved in this process are epithelial to mesenchymal transition (EMT) and epidermal growth factor receptor (EGFR) signalings through the regulation of Yes-associated protein (YAP)/PDZ-binding motif (TAZ) expression. In the current study, we investigated the role of miR-33a family as a (i) modulator of YAP/TAZ expression and (ii) a regulator of EGFR signaling during osteoblast commitments. Starting from the observation on hMSCs and primary osteoblast cell lines (Nh-Ost) in which EMT genes and miR-33a displayed a specific expression, we performed a gain and loss of function study with miR-33a-5p and 3p on hMSCs cells and Nh-Ost. After 24 h of transfections, we evaluated the modulation of EMT and osteoblast genes expression by qRT-PCR, Western blot, and Osteoimage assays. Through bioinformatic analysis, we identified YAP as the putative target of miR-33a-3p. Its role was investigated by gain and loss of function studies with miR-33a-3p on hMSCs; qRT-PCR and Western blot analyses were also carried out. Finally, the possible role of EGFR signaling in YAP/TAZ modulation by miR-33a-3p expression was evaluated. Human MSCs were treated with EGF-2 and EGFR inhibitor for different time points, and qRT-PCR and Western blot analyses were performed. The above-mentioned methods revealed a balance between miR-33a-5p and miR-33a-3p expression during hMSCs osteoblast differentiation. The human MSCs phenotype was maintained by miR-33a-5p, while the maintenance of the osteoblast phenotype in the Nh-Ost cell model was permitted by miR-33a-3p expression, which regulated YAP/TAZ through the modulation of EGFR signaling. The inhibition of EGFR blocked the effects of miR-33a-3p on YAP/TAZ modulation, favoring the maintenance of hMSCs in a committed phenotype. A new possible personalized therapeutic approach to bone regeneration was discussed, which might be mediated by customizing delivery of miR-33a in simultaneously targeting EGFR and YAP signaling with combined use of drugs.

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Section: Discussionmentioning

confidence: 99%

MiR-33a Controls hMSCS Osteoblast Commitment Modulating the Yap/Taz Expression Through EGFR Signaling Regulation

Costa

Carina

Raimondi

et al. 2019

Cells

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“…Furthermore, miR-33a regulation by Twist1 restrained epithelial-to-mesenchymal transition and metastasis in non-small-cell lung carcinoma (NSCLC) (9). Previous research indicates that miR-33a expression is inhibited in various cancer types including NSCLC, gallbladder cancer, hepatocellular carcinoma (HCC), breast cancer, melanoma and pancreatic cancer (9)(10)(11)(12)(13)(14)(15)(16). However, overexpression of miR-33a has been reported in prostate cancer (17).…”

Section: Introductionmentioning

confidence: 99%

Suppression of SIRT6 by miR-33a facilitates tumor growth of glioma through apoptosis and oxidative stress resistance

Chang

Lin²,

et al. 2017

Oncology Reports

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microRNA-33a (miR-33a) belongs to the miR-33 family that is implicated in the progression of various types of cancers. Aberrant expression of miR-33a has been detected in several human cancers, and has been shown to regulate the migration and invasion as well as proliferation and apoptosis of tumor cells. However, the clinical significance and precise mechanisms underlying the dysfunction of miR-33a in glioma have not been well investigated in previous studies. In this study, overexpression of miR-33a was observed in clinical glioma specimens and cell lines. Clinicopathological detection revealed that miR-33a highly expressing patients showed large tumor sized and advanced World Health Organization (WHO) grade as well as reduced overall survival. Furthermore, the results of in vitro experiments confirmed that loss of miR-33a resulted in reduced proliferation and enhanced apoptosis in U251 cells, while miR-33a restoration showed opposite effects in U87 cells. Further studies indicated that miR-33a knockdown restrained tumor growth of glioma in vivo. miR-33a negatively regulated the expression of sirtuin 6 (SIRT6) at both mRNA and protein levels via targeting the 3'UTR of SIRT6 mRNA. SIRT6 was underexpressed and inversely correlated with miR-33a expression in the glioma tissues. Mechanistically, SIRT6 overexpression increased the levels of lactate dehydrogenase (LDH) and reactive oxygen species (ROS) while it reduced cell survival under H2O2 treatment. In addition, SIRT6 restoration led to apoptosis with alterative expression of Bax, Bcl-2, cleaved caspase-8, and inhibition of Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway in glioma. Thus, our studies demonstrated that the deregulation of miR-33a may promote tumor development in human glioma by regulating the expression of its target gene, SIRT6.

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“…5,6 MicroRNAs (miRNAs) have been shown to have regulatory control of over one-third of human protein coding genes, 7 including those regulating collagen 8 and the production of inflammatory mediators. 9 These molecules are small, non-coding RNAs involved in mRNA regulation at a post-transcriptional level, often acting as inhibitors to gene expression. MiRNAs bind to the 3 0 -UTR of target mRNA resulting in, most cases, inhibition of translation or targeted degradation of the mRNA itself.…”

mentioning

confidence: 99%

Effect of micro‐RNA on tenocytes and tendon‐related gene expression: A systematic review

Dubin

Greenberg

Iglinski-Benjamin

et al. 2018

Journal Orthopaedic Research

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The purpose of the review was to synthesize the current literature regarding the effect of miRNA on biological processes known to be involved in tendon and tenocyte development and homeostasis. Using multiple databases, a systematic review was performed with a customized search term crafted to identify any study examining micro-RNA in relation to tendon and/or tenocytes. Results were classified based on the following categories: Gene expression, tenocyte development and differentiation, tendon tissue repair, and tenocyte senescence. A total of 3,112 potentially relevant studies were reviewed, and after exclusion criteria was applied, 15 investigations were included in the final analysis. There were 14 specific miRNA included in this review, with 11 studies reporting on tendon-related gene expression, five reporting on tendon development and/or tenocyte differentiation, six reporting on tendon tissue repair, and five reporting on tenocyte senescence. The miR-29 family was the most commonly reported micro-RNA in the investigation. We also report on a number of micro-RNA which are associated with both positive and negative effects on tendon homeostasis. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

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The microRNA miR-33a suppresses IL-6-induced tumor progression by binding Twist in gallbladder cancer

Cited by 31 publications

References 39 publications

MiR-33a Controls hMSCS Osteoblast Commitment Modulating the Yap/Taz Expression Through EGFR Signaling Regulation

MiR-33a Controls hMSCS Osteoblast Commitment Modulating the Yap/Taz Expression Through EGFR Signaling Regulation

Suppression of SIRT6 by miR-33a facilitates tumor growth of glioma through apoptosis and oxidative stress resistance

Effect of micro‐RNA on tenocytes and tendon‐related gene expression: A systematic review

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