MiR-26a-5p enhances cells proliferation, invasion, and apoptosis resistance of fibroblast-like synoviocytes in rheumatoid arthritis by regulating PTEN/PI3K/AKT pathway

Huang, Zhengping; Xing, Shan; Li, Meng; Deng, Weiming; Wang, Yunqing; Huang, Zhixiang; Huang, Yung-Cheng; Huang, Xiaoyu; Wu, Chi-Wei; Guo, Xin; Pan, Xia; Jiang, Jiawei; Feng, Fan; Li, Tianwang

doi:10.1042/bsr20182192

Cited by 48 publications

(29 citation statements)

References 42 publications

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“…MiR-26a-5p has previously been reported to promote cell proliferation, accelerate G1/S cell cycle transition, and enhance cancer metastasis [ 41 – 43 ]. Moreover, miR-26a-5p upregulation predicts poor prognosis in lung cancer and has been proposed to be used as a potential prognostic biomarker [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Lnc-GAN1 expression is associated with good survival and suppresses tumor progression by sponging mir-26a-5p to activate PTEN signaling in non-small cell lung cancer

Wang

Long

Zhou

et al. 2021

J Exp Clin Cancer Res

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Background Long non-coding RNAs (lncRNAs) play vital roles in the development and progression of non-small-cell lung cancer (NSCLC); however, the role of most lncRNAs in NSCLC remains unknown. This study explored the clinical significance, biological function and underlying mechanism of lnc-GAN1 in NSCLC. Methods With a custom lncRNA microarray we found that lnc-GAN1 is markedly downregulated in NSCLC tissues. Then lnc-GAN1 expression level was measured using qRT-PCR in NSCLC tissues and cell lines. Survival was assessed using the Kaplan-Meier method. The biological functions of lnc-GAN1 in lung cancer cells were evaluated in vitro and in vivo. RNA fluorescence in situ hybridization and subcellular localization assays revealed the subcellular distribution of lnc-GAN1 in cells. Bioinformatic analysis was adopted to predict miRNAs and signaling pathways regulated by lnc-GAN1. RNA immunoprecipitation and Dual-luciferase reporter assays were used to assess the interaction between lnc-GAN1 and miR-26a-5p in lung cancer cells. Results lnc-GAN1 is downregulated in HCC tissues and associated with larger tumor size and poor overall survival and disease-free survival; its ectopic expression suppresses cell proliferation, colony formation, and cell cycle progression and induces apoptosis in NSCLC cells; it also inhibits tumor growth in the NSCLC xenograft model. We further proved that lnc-GAN1 is localized in cytoplasm and transcribed independently from its parental gene GAN. Mechanistically, lnc-GAN1 acts as a sponge for miR-26a-5p by two seed sequences, and the two non-coding RNAs have a negative relationship in NSCLC tissues; we further prove that PTEN is a direct target of miR-26a-5p and lnc-GAN1 inhibits cell cycle signaling pathway by activating PTEN, whose expression level correlated negatively with miR-26a-5p level but positively with lnc-GAN1 level in NSCLC samples. Conclusions Lnc-GAN1 is downregulated and associated with poor survival of NSCLC patients, and mechanistically acts as a tumor suppressor via sponging and inhibiting miR-26a-5p to upregulate PTEN. This study provides a potential prognostic biomarker and treatment target for NSCLC.

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Section: Discussionmentioning

confidence: 99%

Lnc-GAN1 expression is associated with good survival and suppresses tumor progression by sponging mir-26a-5p to activate PTEN signaling in non-small cell lung cancer

Wang

Long

Zhou

et al. 2021

J Exp Clin Cancer Res

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“…First, the PI3K/AKT signaling pathway has been showed to articipate in the pathogenesis of RA and may serve as an important target in RA therapies. For example, Huang et al demonstrated that miR-26a-5p enhances cells proliferation, invasion, and apoptosis resistance of FLS in RA by regulating PTEN/PI3K/AKT pathway [32]. Similarly, Li reported that cinnamaldehyde attenuates the progression of RA through down-regulation of PI3K/AKT signaling pathway [33].…”

Section: Discussionmentioning

confidence: 99%

Long Non-coding RNA LINC02085 Mediates Cell Growth and Inflammatory Response of Fibroblast-Like Synoviocytes by Activating PI3K/AKT Signals in Rheumatoid Arthritisis

Wen¹,

Liu²,

Wang³

et al. 2020

Preprint

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Background: The present study explored the possible functions and the underlying mechanism of Long Non-coding RNA LINC02085 in rheumatoid arthritis (RA). Methods: Peripheral blood mononuclear cells (PBMCs) were collected from patients with RA. Primary fibroblast-like synoviocytes (FLS) were separated from synovial tissues and was established cell lines, then cultured for subsequent cell experiments by transfecting different vectors. The RT-qPCR analysis was employed for evaluating the levels of LINC02085 in the PBMCs and RA-FLS. ELISA analysis was employed to detect the levels of inflammatory cytokines. CCK8 assay, migration and invasion assays were used to evaluate the proliferation, migration and invasion abilities of cells, respectively. Besides, the levels of the the PI3K/AKT pathway-related proteins were measured by WB and IF. Spearman correlation analysis, association rule analysis, logistic regression analysis were used to assess the correlation between LINC02085 and clinical parameters. Results: The expression level of LINC02085 was significant high in patients with RA, and positively associated with age, ESR, CRP, RF, CCP and DAS28. Moreover, logistic regression analysis indicated that ESR, CRP, RF and DAS28 were risk factors for LINC02085. We found that LINC02085 was upregulated in RA -FLS and TNF-αstimulated. And overexpression of LINC02085 could promote proliferation, migration and invasion induced by TNF-α, through upregulating the levels of TNF-αand TNFAIP2 and promoting the activation of PI3K/AKT pathway. Whereas knockdown of LINC02085 received the opposite results. Conclusion: In conclusion, the present study revealed that LINC02085 could regulate cell growth and inflammatory response of RA-FLS by activating the PI3K/ AKT signaling pathway, subsequently playing important roles in promoting the occurrence and development of RA.

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“…It has been reported PTEN/PI3K/AKT signaling was closely related to cell proliferation and apoptosis [14][15][16][17][18]. Next, we explored the effect of miRNA-425-5p on PTEN/PI3K/AKT signaling.…”

Section: Mir-425-5p Activates Pten/pi3k/akt Signalingmentioning

confidence: 99%

miRNA-425-5p enhances lung cancer growth via the PTEN/PI3K/AKT signaling axis

et al. 2020

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Background: miRNAs regulate a multitude of cellular processes and their aberrant regulation is linked to human cancer. However, the role of miR-425-5p in lung cancer (LCa) is still largely unclear. Here, we explored the role of miR-425-5p during LCa tumorigenesis. Methods: Cell proliferation was evaluated by cell counting Kit-8 and colony formation assay. Western blot and realtime PCR were accordingly used to detect the relevant proteins, miRNA and gene expression. Luciferase reporter assays were used to illustrate the interaction between miR-425-5p and PTEN. Results: We demonstrate that miR-425-5p is overexpressed in LCa tissue and enhances the proliferative and colony formation capacity of the LCa cell lines A549 and NCI-H1299. Through predictive binding assays, PTEN was identified as a direct gene target and its exogenous expression inhibited the pro-cancer effects of miR-425-5p. Through its ability to down-regulate PTEN, miR-425-5p activated the PI3K/AKT axis. Conclusion: We conclude that miR-425-5p promotes LCa tumorigenesis through PTEN/PI3K/AKT signaling.

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MiR-26a-5p enhances cells proliferation, invasion, and apoptosis resistance of fibroblast-like synoviocytes in rheumatoid arthritis by regulating PTEN/PI3K/AKT pathway

Cited by 48 publications

References 42 publications

Lnc-GAN1 expression is associated with good survival and suppresses tumor progression by sponging mir-26a-5p to activate PTEN signaling in non-small cell lung cancer

Lnc-GAN1 expression is associated with good survival and suppresses tumor progression by sponging mir-26a-5p to activate PTEN signaling in non-small cell lung cancer

Long Non-coding RNA LINC02085 Mediates Cell Growth and Inflammatory Response of Fibroblast-Like Synoviocytes by Activating PI3K/AKT Signals in Rheumatoid Arthritisis

miRNA-425-5p enhances lung cancer growth via the PTEN/PI3K/AKT signaling axis

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