The lncRNA MALAT1 contributes to non-small cell lung cancer development via modulating miR-124/STAT3 axis.

lncRNAs can exert many biological effects in several cancer types. MALAT1 is a kind of lncRNA which is greatly overexpressed in several tumors including non-small cell lung cancer (NSCLC). However, the mechanism of MALAT1 in NSCLC still remains unclear. In our current study, we concentrated on the biological mechanism of MALAT1 in NSCLC. It was observed that MALAT1 was significantly upregulated in five human NSCLC cells including A549, H23, H522, H1299, and H460 cells compared to normal bronchial epithelial cell line 16HBE cells. On the contrary, miR-124 was remarkably downregulated, which indicated a potential negative correlation between miR-124 and MALAT1. MALAT1 inhibition can increase miR-124 expression in A549 and H460 cells. In addition, miR-124 mimics were able to repress MALAT1 expression and miR124 inhibitors can promote MALAT1 levels. Then it was found that shMALAT1 can inhibit NSCLC cell proliferation, colony formation and apoptosis, which can be reversed by miR-124 inhibitors. Bioinformatic analysis predicted the correlation between miR-124 and MALAT1. In addition, STAT3 was found to be a novel mRNA target of miR-124. Downregulation of MALAT1 can inhibit NSCLC development by enhancing miR-124 and decreasing STAT3 expression. We speculated that MALAT1can act as a competing endogenous lncRNA (ceRNA) to modulate miR-124/STAT3 in NSCLC. Taken these together, we revealed that MALAT1/miR-124/STAT3 was involved in NSCLC development.

Li S ，Mei Z ，Hu HB ，Zhang X ... -  《-》

H19 promotes non-small-cell lung cancer (NSCLC) development through STAT3 signaling via sponging miR-17.

LncRNAs can exhibit crucial roles in the development of multiple cancers, including non-small cell lung cancer (NSCLC). Currently, we investigated the role of lncRNA H19 in NSCLC. In our study, it was found that H19 was upregulated in A549 and H1299 cells compared to normal lung epithelial BEAS-2B cells. Meanwhile, we observed that miR-17 was downregulated in NSCLC cell lines. Inhibited H19 can suppress the growth, migration, and invasion of NSCLC cells and bioinformatics search was performed to predict the correlation between H19 and miR-17. Overexpression of miR-17 was able to inhibit the progression of NSCLC cells while reversely miR-17 inhibitors reversed this process. In addition, signal transducers and activators of transcription (STAT3), as an mRNA target of miR-17, was presented in our research. Moreover, we discovered that H19 demonstrated its biological functions via regulating miR-17 and STAT3 in vitro. Silencing H19 greatly increased STAT3 expression by sponging miR-19 in vitro. It was hypothesized that H19 may serve as a competing endogenous RNA (ceRNA) to modulate STAT3 by attaching miR-17 in lung cancer. In summary, our findings indicated that H19/miR-17/STAT3 axis participated in NSCLC development. H19 could be regarded as a significant prognostic biomarker in NSCLC progression.

Huang Z ，Lei W ，Hu HB ，Zhang H ，Zhu Y ... -  《-》

Long non-coding RNA MALAT1 promotes oral squamous cell carcinoma development via microRNA-125b/STAT3 axis.

Oral squamous cell carcinoma (OSCC), as the most common type of oral cancer, is responsible for almost 3% of all malignant tumors worldwide. Non-coding RNAs such as lncRNAs and microRNAs have been involved in many cancers including OSCC. Recently, lncRNA metastasis-associated lung adenocarcinoma transcript-1 (MALAT1) has been reported to play an oncogenic role in OSCC metastasis. However, the underlying mechanism of MALAT1 in regulating OSCC progression remains unclear. The aim of this study was to investigate the specific role of MALAT1 in OSCC development. It was observed that MALAT1 was upregulated in OSCC cell lines. Inhibition of MALAT1 can prevent OSCC proliferation while overexpressing MALAT1 promoted OSCC progression. In addition, bioinformatics search was used to identify that miR-125b was a direct target of MALAT1, which indicated a negative correlation between MALAT1 and miR-125b. Besides these, STAT3 was predicted as a binding target of miR-125b in OSCC. Overexpression of MALAT1 was able to suppress the tumor inhibitory effect of miR-125b mimics via upregulating STAT3. Moreover, the function of MALAT1 in OSCC development was further investigated by using in vivo assays. The established nude mice models revealed that downregulated MALAT1 greatly inhibited OSCC tumor growth and reversely upregualated MALAT1 promoted OSCC development via miR-125b/STAT3 axis, respectively. In conclusion, MALAT1 can function as a competing endogenous RNA (ceRNA) to modulate STAT3 expression by absorbing miR-125b in OSCC and could be used as a novel therapeutic target in OSCC diagnosis and treatment.

Chang SM ，Hu WW 《-》

MicroRNA-142-3p/MALAT1 inhibits lung cancer progression through repressing β-catenin expression.

MALAT1 is well documented to be highly expressed in non-small cell lung cancer (NSCLC) and its overexpression closely associates the malignant phenotype of NSCLC cells and poor prognosis of NSCLC patients. MALAT1 is also identified to enhance β-catenin expression and under the negative regulation of miR-142-3p. However, the role of miR-142-3p/MALAT1/β-catenin in the occurrence and development of NSCLC remains unclear. The objective of this study was to explore it. The results showed that miR-142-3p expression was reduced in NSCLC tissues, while β-catenin and MALAT1 expression levels were elevated. MTT, transwell chamber, flow cytometry assays demonstrated that up-regulation of miR-142-3p with mimic transfection significantly inhibited the proliferation, migration and promoted the apoptosis of NSCLC H1299 cells, and induced a G0/G1 phase arrest and S phase reduction. Besides, miR-142-3p negatively decreased MALAT1 expression as detected by RT-PCR and luciferase reporter assays. Moreover, up-regulation of miR-142-3p decreased β-catenin expression through down-regulating MALAT1 in H1299 cells. And in vivo experiment showed that miR-142-3p up-regulation, as well as the knockdown of either β-catenin or MALAT1 significantly reduced the tumorigenesis of NSCLC cells. Taken together, our study makes clear that miR-142-3p functions as a tumor suppressor in NSCLC progression through inhibiting MALAT1/β-catenin signaling.

Liu J ，Tian W ，Zhang W ，Jia Y ，Yang X ，Wang Y ，Zhang J ... -  《-》

The long noncoding RNA NEAT1 contributes to hepatocellular carcinoma development by sponging miR-485 and enhancing the expression of the STAT3.

Accumulating evidence has supported the significance of lncRNAs in tumorigenesis. Recently, some studies indicate the oncogenic role of lncRNA Nuclear Enriched Abundant Transcript 1 (NEAT1) in hepatocellular carcinoma (HCC). In our present study, we focused on the biological mechanisms through which NEAT1 can regulate HCC development. We found that NEAT1 was greatly upregulated in human HCC cell lines including Huh7, Hep3B, HepG2, Bel-7404, and SK-Hep1 cells compared to the normal human liver cell line LO2. In addition, we observed that miR-485 was significantly downregulated in HCC cells. It was implied that miR-485 was increased by sh-NEAT1 and miR-485 can modulate NEAT1 expression negatively. Meanwhile, NEAT1inhibiton can repress HCC growth, migration, and invasion capacity in HepG2 and Hep3B cells. Through performing bioinformatic analysis, dual-luciferase reporter test, RNA-binding protein immunoprecipitation, and RNA pull-down assay, miR-485 was confirmed as a interacting target of NEAT1. Additionally, STAT3 was recognized as a direct target of miR-485 and miR-485 mimics can inhibit STAT3 expression. It was demonstrated that NEAT1 can increase STAT3 levels while miR-485 mimics can repress STAT3. Moreover, we found that sh-STAT3 was able to restrain HCC cell migration and invasion process. NEAT1 can act as a competing endogenous lncRNA (ceRNA) to regulated STAT3 by sponging miR-485 in HCC. Taken these together, NEAT1 can be used as an important biomarker in HCC diagnosis and treatment.

Zhang XN ，Zhou J ，Lu XJ 《-》