LncRNA MALAT1 accelerates non-small cell lung cancer progression via regulating miR-185-5p/MDM4 axis.

Non-small cell lung cancer (NSCLC) is the commonest malignancy with high death rate around the world. LncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is greatly overexpressed in multifarious cancers, including NSCLC. However, the precise mechanism of MALAT1 in NSCLC tumorigenesis is blurry. This paper aims to investigate the theory of MALAT1 action in NSCLC progression. The levels of MALAT1, microRNA (miR)-185-5p, and mouse double minute 4 protein (MDM4) were measured by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Cell proliferation and apoptosis were, respectively, determined by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay, and flow cytometry. Cell migratory and invasive abilities were inspected by transwell assay. The binding relationship between miR-185-5p and MALAT1 or MDM4 was confirmed by dual-luciferase reporter assay. The impacts of MALAT1 on tumor growth in vivo were measured by a xenograft experiment. We found MALAT1 and MDM4 were upregulated and MALAT1 positively regulated the MDM4 expression. MALAT1 and MDM4 deletion significantly hindered the proliferation, metastasis, and expedited the apoptosis of NSCLC cells. MDM4 overexpression partly overturned the influence of MALAT1 downregulation on cell development. Moreover, miR-185-5p, as a target of MALAT1, could directly target MDM4, and miR-185-5p upregulation exerted inhibitory effects on NSCLC cells. Besides, knockdown of MALAT1 inhibited tumor growth in vivo through miR-185-5p/MDM4 axis in NSCLC. Collectively, MALAT1 contributed to proliferation, migration, invasion, and impeded apoptosis by regulating the MDM4 expression mediated by miR-185-5p in NSCLC cells.

Wang D ，Zhang S ，Zhao M ，Chen F ... -  《Cancer Medicine》

Long non-coding RNA MALAT1 regulates proliferation, apoptosis, migration and invasion via miR-374b-5p/SRSF7 axis in non-small cell lung cancer.

Song J ，Su ZZ ，Shen QM 《-》

LncRNA MALAT1 promotes migration and invasion of non-small-cell lung cancer by targeting miR-206 and activating Akt/mTOR signaling.

Tang Y ，Xiao G ，Chen Y ，Deng Y ... -  《-》

LncRNA SNHG1 influences cell proliferation, migration, invasion, and apoptosis of non-small cell lung cancer cells via the miR-361-3p/FRAT1 axis.

Non-small-cell lung cancer (NSCLC) is the most lethal type of cancer. Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been identified as crucial regulators in the development of NSCLC. The aim of our study was to explore the molecular mechanism of SNHG1 to enable better treatment for NSCLC patients. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression of Small nucleolar RNA host gene 1 (SNHG1), miR-361-3p and frequently rearranged in advanced T-cell lymphomas 1 (FRAT1). The protein level of FRAT1 was measured by western blot assay. Cell proliferation was evaluated by methyl thiazolyl tetrazolium (MTT) assay. Cell apoptosis was assessed by flow cytometry assay. The number of migrated and invaded cells were counted by transwell assay. The relationship between miR-361-3p and SNHG1 or FRAT1 was confirmed by dual-luciferase reporter assay. Our results indicated that SNHG1 and FRAT1 were highly expressed in NSCLC tissues and cells. SNHG1 silencing inhibited proliferation, induced apoptosis and blocked migration and invasion of NSCLC cells. Also, FRAT1 downregulation suppressed proliferation, promoted apoptosis and hindered migration and invasion of NSCLC cells. Further, FRAT1 could recover the effects of SNHG1 silencing on proliferation, apoptosis, migration and invasion of NSCLC cells. SNHG1 sponged miR-361-3p and negatively regulated miR-361-3p expression. Meanwhile, miR-361-3p targeted FRAT1 and inversely modulated FRAT1 expression. In addition, miR-361-3p inhibition abated the effect of SNHG1 knockdown on FRAT1 expression. In conclusion, LncRNA SNHG1 promoted the proliferation, repressed apoptosis and enhanced migration and invasion of NSCLC cells by regulating FRAT1 expression via sponging miR-361-3p.

Li X ，Zheng H 《-》

LncRNA SNHG1 contributes to the cisplatin resistance and progression of NSCLC via miR-330-5p/DCLK1 axis.

Long non-coding RNAs (lncRNAs) are involved in the occurrence and progression of multiple cancers, including non-small cell lung cancer (NSCLC). Herein, we explored the exact role and underlying mechanism of lncRNA small nucleolar RNA host gene 1 (SNHG1) in NSCLC. The levels of SNHG1, microRNA-330-5p (miR-330-5p) and doublecortin-like kinase 1 (DCLK1) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was carried out to measure the chemoresistance and proliferation of NSCLC cells. The metastasis and apoptosis of NSCLC cells were examined by transwell migration and invasion assays and flow cytometry. Western blot assay was conducted to detect the levels of proliferation-associated proteins and DCLK1. The interaction between miR-330-5p and SNHG1 or DCLK1 was predicted by StarBase and microT_CDS databases. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to validate these interactions. In vivo chemosensitivity experiment was conducted to assess the function of SNHG1 in the chemoresistance of NSCLC in vivo. SNHG1 was dramatically up-regulated in cisplatin (DDP)-resistant NSCLC tissues and cells. SNHG1 promoted the DDP resistance and malignant behaviors of NSCLC cells. SNHG1 functioned through targeting miR-330-5p, and si-SNHG1-mediated effects in NSCLC cells were attenuated by the addition of in-miR-330-5p. DCLK1 messenger RNA (mRNA) could directly bind to miR-330-5p, and miR-330-5p acted as a tumor suppressor in NSCLC through down-regulating DCLK1. SNHG1 silencing elevated the DDP sensitivity of NSCLC cells in vivo. SNHG1 elevated DDP resistance and malignant potential of NSCLC cells through elevating the level of DCLK1 via sponging miR-330-5p.

Ge P ，Cao L ，Zheng M ，Yao Y ，Wang W ，Chen X ... -  《-》