Long non-coding RNA MALAT-1 modulates metastatic potential of tongue squamous cell carcinomas partially through the regulation of small proline rich proteins

Abstract

BackgroundWe previously described several abnormally expressed long non-coding RNA (lncRNA) in tong squamous cell carcinomas (TSCCs) that might be associated with tumor progression. In the present study, we aimed to investigate the role of abnormally expressed metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) lncRNA in the metastatic potential of TSCC cells and its molecular mechanisms.MethodsExpression levels of MALAT-1 lncRNA were examined via quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in 127 TSCC samples as well as paired adjacent normal tissues and lymph node metastases (if exist). Lentiviral vectors expressing short hairpin RNA (shRNA) were used to knock down the expression of MALAT1 gene in two TSCC cell lines (CAL27 and SCC-25) with relatively higher MALAT-1 expression. Proliferational ability of the TSCC cells was analyzed using water soluble tetrazolium-1 (WST-1) assay. Metastatic abilities of TSCC cells were estimated in-vitro and in-vivo. We also performed a microarray-based screen to identify the genes influenced by MALAT-1 alteration, which were validated by real-time PCR analysis.ResultsExpression of MALAT-1 lncRNA was enhanced in TSCCs, especially in those with lymph node metastasis (LNM). Knockdown (KD) of MALAT-1 lncRNA in TSCC cells led to impaired migration and proliferation ability in-vitro and fewer metastases in-vivo. DNA microarray analysis showed that several members of small proline rich proteins (SPRR) were up-regulated by KD of MALAT-1 lncRNA in TSCC cells. SPRR2A over-expression could impair distant metastasis of TSCC cells in-vivo.ConclusionEnhanced expression of MALAT-1 is associated with the growth and metastatic potential of TSCCs. Knock down of MALAT-1 in TSCCs leads to the up-regulation of certain SPRR proteins, which influenced the distant metastasis of TSCC cells.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2735-x) contains supplementary material, which is available to authorized users.

High expression of long non-coding RNA MALAT1 in breast cancer is associated with poor relapse-free survival

“…The MALAT1 gene is highly conserved across mammals, suggesting that it may have important biological implications [9]. Evidence suggests that MALAT1 may act like an oncogene in several malignancies, including lung cancer [17, 24], pancreatic cancer [19], liver cancer [20], bladder cancer [25], prostate cancer[26], colon cancer [27, 28], renal cell carcinoma [18], and oral squamous cell carcinomas [29, 30]. Lowering MALAT1 expression in hepatocellular carcinoma cells resulted in reduced cell proliferation and colony formation [20].…”

Functions and regulatory mechanisms of metastasis‐associated lung adenocarcinoma transcript 1

“…As one of the first identified cancer‐associated lncRNAs, MALAT1 was reported to be overexpressed in gastric cancer (Chen, Liu, Wang et al, 2017), breast cancer (Arun et al, ), prostate cancer (Ren et al, ), cervical cancer (Sun, Qin et al, ), acute myeloid leukemia (Chen, Nagel et al, 2018), medullary thyroid cancer (Chu, Hardin, Schneider, Chen, & Lloyd, ), choriocarcinoma (Shi, Wang, & Yin, ), gallbladder cancer (Sun et al, ), pancreatic cancer (Xie et al, 2017), multiple myeloma (Liu, Wang et al, ), ovarian cancer (Wu et al, 2017), T and natural killer cell lymphoma (Kim, Kim, Yang, Kim, & Yoon, ), acute monocytic leukemia (Huang, Liu et al, ), endometrial stromal sarcoma (Yamada et al, ), myeloma (Cho et al, ), clear cell renal cell carcinoma (Zhang, Yang, Chen, Che, & Zheng, ), esophageal squamous cell carcinoma (Hu et al, ), glioma (Ma, Wang, Li et al, ), osteosarcoma (Cai et al, ), neuroblastoma (Tee et al, ), tongue squamous cell carcinomas (Fang et al, ), hilar cholangiocarcinoma (Tan, Huang, & Li, ), mantle cell lymphoma (Wang, Zhu et al, ), and other tumor tissues. It has been reported that MALAT1 is involved in the regulation of tumor proliferation, apoptosis, invasion, metastasis, and angiogenesis.…”

World Workshop on Oral Medicine VII: Clinical evidence of differential expression of lncRNAs in oral squamous cell carcinoma: A scoping review

“…The expression of MALAT1 has been addressed by six studies finding a significant overexpression in four of these. Three studies addressing TSCC (overall 159 patients) found significant overexpression (Fang et al., , ; Liang, Liang, Ouyang, Li, & Yi, ). When dealing with OSCC, two studies with similar sample size showed contrasting results, as only one was able to find significant DE (Arunkumar, Deva Magendhra Rao et al., ; Zhou et al., ).…”