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 《-》

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 ... -  《-》

Long noncoding RNA SNHG12 promotes the progression of cervical cancer via modulating miR-125b/STAT3 axis.

Increasing evidence showed that long noncoding RNAs (lncRNAs) played an important role in the occurrence and development of tumors. To date, lncRNA small nucleolar RNA host gene 12 (SNHG12) has revealed an oncogenic role in various tumors. However, the role of SNHG12 in cervical cancer is still unclear. Therefore, we focused on the biological function and molecular mechanism of SNHG12 in the tumorigenesis of cervical cancer. In this study, the expression of miR-125b was observably downregulated in cervical cancer cells. Meanwhile, the expression of SNHG12 was obviously upregulated in cervical cancer cell lines (HeLa, SiHa, Caski, C4-1, and C33A) compared with the immortalized cervical epithelial cells. The further assay showed that miR-125b was a target of SNHG12 in cervical cancer. Moreover, a negative relationship between miR-125b and SNHG12 was found in cervical cancer. In addition, SNHG12 inhibition restrained the proliferation, migration, and invasion of cervical cancer cells. Meanwhile, miR-125b mimics repressed the expression of signal transducer and activator of transcription 3 (STAT3). The further assay showed that STAT3 was a target of miR-125b in cervical cancer. In addition, sh-STAT3 repressed the migration and invasion of cervical cancer cells. Furthermore, it showed that miR-125b inhibitors reversed STAT3 expression restrained by the reduction of SNHG12 expression. In general, SNHG12 modulated STAT3 by sponging miR-125b in cervical cancer and played an important role in the development of cervical cancer.

Jin XJ ，Chen XJ ，Zhang ZF ，Hu WS ，Ou RY ，Li S ，Xue JS ，Chen LL ，Hu Y ，Zhu H ... -  《-》

Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 regulates the expression of Gli2 by miR-202 to strengthen gastric cancer progression.

Gastric cancer (GC) is one of the most common malignancies and ranks the second leading cause of cancer death worldwide. Some studies had reported the tumor-promoting effects of long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) as a competing endogenous RNA (ceRNA) by sponging to microRNAs. However, the molecular mechanism of ceRNA regulatory pathway involving MALAT1 in GC remains unclear. MALAT1 and miR -202 expression was detected by quantitative real time PCR (qRT-PCR) in 60 gastric cancer tissues and adjacent normal tissues, CCK8 cell proliferation assays, cell cycle analysis and cell apoptosis assays were performed to detect the GC cell proliferation and apoptosis. The mRNA and protein levels of Gli2 were analyzed by quantitative real-time PCR and Western blotting assays. Furthermore, using online software, luciferase reporter assays, RNA immunoprecipitation (RIP) and RNA pulldown assays demonstrated miR-202 was a target of MALAT1. We found that MALAT1 was upregulated in GC tissues and higher MALAT1 expression was correlated with larger tumor size, lymph node metastasis, and TNM stage. Moreover, we revealed that MALAT1 was a direct target of miR-202 and knockdown of MALAT1 significantly decreased the expression of Gli2 through negatively regulating miR-202. In addition, knockdown of Malat1 inhibited GC cells proliferation, S-phase cell number, and induced cell apoptosis via negatively regulating miR-202 in vitro. Our results elucidated MALAT1/miR-202/Gli2 regulatory pathway, which maybe contribute to a novel therapeutic strategy for GC patients.

Zhang Y ，Chen Z ，Li MJ ，Guo HY ，Jing NC ... -  《-》

Long non-coding RNA MALAT1 aggravates human retinoblastoma by sponging miR-20b-5p to upregulate STAT3.

Retinoblastoma (RB) is an uncommon childhood carcinoma of the developing retina. Long non-coding RNA (lncRNA) metastasis associated lung adenocarcinoma transcript 1 (MALAT1), microRNA-20b-5p (miR-20b-5p) and signal transducer and activator of transcription 3 (STAT3) was revealed to partake in RB. But their relationship was still to be investigated, so we intended to discuss the specific interaction of MALAT1, miR-20b-5p and STAT3 in RB. By RNA isolation and quantitation, we measured the MALAT1 expression in RB tissues and cell lines. Then, to determine the influence of MALAT1 on RB cells, RB cells were transfected with siRNA-MALAT1 or pcDNA-MALAT1. The interplay among MALAT1, miR-20b-5p and STAT3 were evaluated through dual luciferase reporter gene assay and RNA pull-down after RB cells treated with siRNA/pcDNA-MALAT1 or/and miR-20b-5p mimic/inhibitor. The influence of their interaction on cells was evaluated by cell counting kit-8, EdU assay and flow cytometry. Finally, the involvement of MALAT1 in tumorigenesis was elucidated in vivo. Both RB tissues and cells showed highly expressed MALAT1. When MALAT1 was downregulated, RB cell proliferation was hindered and apoptosis was accelerated. MALAT1 sponged miR-20b-5p and upregulated STAT3. Silencing MALAT1 or overexpressing miR-20b-5p inhibited proliferation and promoted apoptosis in RB cells. The tumor growth of nude mice treated with siRNA-MALAT1 was inhibited. MALAT1 could increase proliferation and reduce apoptosis by sponging miR-20b-5p to upregulate STAT3 in RB cells. Therefore, MALAT1 might be a latent target in the RB treatment.

Wang L ，Zhang Y ，Xin X 《-》