Smad3-related miRNAs regulated oncogenic TRIB2 promoter activity to effectively suppress lung adenocarcinoma growth

Lu²,

et al. 2020

Bioscience Reports

Correspondence:Ping Guo (abrseg@163.com) Objective: X inactivate-specific transcript (XIST) is an attractive long noncoding RNA (lncRNA) functioning as an indicator of various human tumors, including laryngeal squamous cell carcinoma (LSCC). The present study was conducted to explore a novel regulatory network of lncRNA XIST in LSCC cells. Materials and methods: Quantitative real-time polymerase chain reaction (QRT-PCR) was used to detect the expression levels of XIST, miR-125b-5p and TRIB2 in LSCC cells and tissues. Cell proliferation, apoptosis, migration and invasion were detected by Cell Counting Kit-8 (CCK-8), flow cytometry and Transwell assays, separately. The relationship among XIST, miR-125b-5p and tribbles homolog 2 (TRIB2) was predicted by starBase v2.0 or Tar-getScan and confirmed by Dual-luciferase reporter assay. The TRIB2 protein expression was quantified by Western blot assay. Murine xenograft model was utilized to validate the role of XIST in vivo. Results: XIST was notably up-regulated in LSCC tissues and cells, and the high level of XIST was associated with the low survival rate of LSCC patients. XIST knockdown markedly repressed cell proliferation, migration and invasion and promoted the apoptosis of LSCC cells and the effects were antagonized by loss of miR-125b-5p. MiR-125b-5p was a target of XIST in LSCC cells, and it could bind to TRIB2 as well. Moreover, XIST-loss-induced down-regulation of TRIB2 could be significantly reversed by miR-125b-5p knockdown. XIST promoted the growth of LSCC tumor in vivo. Conclusion: LncRNA XIST promoted the malignance of LSCC cells partly through competitively binding to miR-125b-5p, which in turn increased TRIB2 expression.

Section: Discussionmentioning

confidence: 99%

LncRNA XIST promotes the progression of laryngeal squamous cell carcinoma via sponging miR-125b-5p to modulate TRIB2

Lu²,

et al. 2020

Bioscience Reports

Cancer Biology & Therapy

“…After 6-7 weeks, the lungs were dissected, and hematoxylin-eosin staining (HE) was performed as described previously. 33 Statistics SPSS Statistics Client 22 (IBM) software was performed to analyze the significance of all results. ANOVA was used to compare different groups with respect to continuous variables.…”

Section: Injection Of Cells Into the Nude Mice Via Tail Veinmentioning

confidence: 99%

MiR-320a effectively suppresses lung adenocarcinoma cell proliferation and metastasis by regulating STAT3 signals

et al. 2017

Self Cite

MicroRNAs play important roles in tumorigenesis of various types of cancers. MiR-320a can inhibits cell proliferation of some cancers, but the biologic roles of miR-320a in lung cancer need to be further studied. Here, we investigated the roles of miR-320a in suppressing the proliferation of lung adenocarcinoma cells. MiR-320a treatment was found to effectively suppress LTEP-a-2 and A549 cell proliferation, and induce more apoptotic cells with irradiation treatment compared with control treatment. Our results also showed that miR-320a, as a novel miRNA, directly regulated signal transducer and activator of transcription 3 (STAT3) and its signals, such as Bcl ¡ 2, Bax, and Caspase 3. The siRNA-inhibited STAT3 levels further proved its roles in regulating STAT3 signals. Moreover, miR-320a treatment effectively suppressed cancer cell growth in mice xenografts compared with controls, and significantly inhibited cell migration in vitro and in vivo. Our findings collectively demonstrated that miR-320a, by directly regulating STAT3 signals, not only suppressed cell proliferation and metastasis, but also enhanced irradiation-induced apoptosis of adenocarcinomia cells.Abbreviations: GFP, green fluorescent protein; HE, hematoxylin-eosin staining; miRNAs, microRNAs; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; NSCLC, Non-small cell lung cancer; STAT3, signal transducer and activator of transcription 3

J Cellular Molecular Medi

“…32 Further study has revealed that deregulation of miR-206 occurs in lung adenocarcinoma correlating with poor prognosis and survival. 33 Chen et al have found miR-206 regulates cisplatin resistance and EMT in human lung adenocarcinoma cells partly by targeting Met. 34 In addition, miR-206 plays a role, involved in the invasion and metastasis of lung cancer, 35 in HGF-induced gefitinib-resistant human lung cancer cells through inhibition of c-Met signalling and EMT.…”

mentioning

confidence: 99%

Reciprocal regulation of miR‐206 and IL‐6/STAT3 pathway mediates IL6‐induced gefitinib resistance in EGFR‐mutant lung cancer cells

Yang

Wang

Chang³

et al. 2019

Persistently activated IL‐6/STAT3 pathway promotes acquired resistance to targeted therapy with epidermal growth factor receptor‐tyrosine kinase inhibitors (EGFR‐TKIs) in non–small‐cell lung cancer (NSCLC) treatment. miR‐206 has been verified to be dysregulated and plays as a negative regulator in lung cancer. However, whether miR‐206 may overcome IL6‐induced gefitinib resistance in EGFR‐mutant lung cancer remains elusive. In this study, we investigated the role of miR‐206 in IL6‐induced gefitinib‐resistant EGFR‐mutated lung cancer cell lines. We showed that forced miR‐206 expression restored gefitinib sensitivity in IL6‐induced gefitinib‐resistant EGFR‐mutant lung cancer cells by inhibiting IL6/JAK1/STAT3 pathway. Specifically, mechanistic investigations revealed that miR‐206 blocked IL‐6/STAT3 signalling via directly targeting the 3'‐UTR of intracellular IL‐6 messenger RNA. Moreover, IL‐6 induced miR‐206 down‐regulation by reducing the cropping process of primary miR‐206 (pri‐miR‐206) into the Drosha/DGCR8 complex. Taken together, our findings reveal a direct role of miR‐206 in regulating IL‐6/STAT3 pathway and contrarily activated IL‐6/STAT3 signalling mediates the miR‐206 maturation process in gefitinib‐resistant EGFR‐mutant lung cancer cells.