LncRNA SNHG20 contributes to cell proliferation and invasion by upregulating ZFX expression sponging miR‐495‐3p in gastric cancer

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Abstract

Long noncoding RNAs (lncRNAs) exert key regulators in cancer development and progression. The functional significance of lncRNA small nucleolar RNA host gene 20 (SNHG20) was reported in gastric cancer (GC); however, the underlying molecular mechanism in GC development is largely unknown. Here, our results showed that the lncRNA SNHG20 expression was significantly higher in GC tissues compared with adjacent normal tissues by quantitative real-time PCR (qRT-PCR) analysis. Higher lncRNA SNHG20 expression was highly associated with tumor size and lymphatic metastasis of patients. Patients with higher lncRNA SNHG20 expression predicted a short disease-free survival (DFS) and overall survival (OS). Furthermore, lncRNA SNHG20 expression negatively associated with miR-495-3p expression and regulated miR-495-3p expression. Function assays confirmed that lncRNA SNHG20 knockdown using RNA interference suppressed cell proliferation and invasion of GC by negatively regulating miR-495-3p expression. Moreover, we demonstrated that lncRNA SNHG20 inhibited zinc finger protein X-linked (ZFX) expression by negatively miR-495-3p expression in GC cells. In vivo, the current study also indicated that lncRNA SNHG20 knockdown reduced the tumor growth by downregulating ZFX expression. Thus, our results implied that inhibition of SNHG20/miR-495-3p/ZFX axis may provide valuable target for GC treatment.

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Long non-coding RNA MEG3 functions as a competing endogenous RNA to regulate gastric cancer progression

Weizhao Peng, Shuang Si, Qingxia Zhang … (2015)

Background Long noncoding RNAs (lncRNAs) have recently emerged as important regulators in governing fundamental biological processes, and many of which are likely to have functional roles in tumorigenesis. Maternally expressed gene 3 (MEG3) gene encodes a lncRNA whose expression is lost in an expanding list of primary human tumors and tumor cell lines, however its biological role and regulatory mechanism in gastric cancer (GC) development and progression are poorly defined. Methods Quantitative RT-PCR analysis was used to determine whether aberrant MEG3 expression was associated with GC patients pTNM stage and pM state. Furthermore, the effect of ectopic expression of MEG3 on cell proliferation, migration, invasion and cell apoptosis was assessed by using CCK-8, wound healing, transwell invasion assays and flow cytometric analysis, respectively, in GC cell lines HGC-27 and MGC-803. Moreover, the competing endogenous RNA (ceRNA) activity of MEG3 on miR-181a was investigated via luciferase reporter assay and immunoblot analysis. Results MEG3 is decreased in GC patients and cell lines, and its expression was associated with metastatic GC. Furthermore, ectopic expression of MEG3 in HGC-27 and MGC-803 cells inhibited cell proliferation, migration, invasion, and promoted cell apoptosis, which might be due to MEG3 sequestering oncogenic miR-181 s in GC cells. Furthermore, MEG3 could up-regulated Bcl-2 via its competing endogenous RNA (ceRNA) activity on miR-181a. Conclusions These findings suggest that lncRNA MEG3, a ceRNA of miR-181 s, could regulate gastric carcinogenesis and may serve as a potential target for antineoplastic therapies.

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Competing endogenous RNA networks and gastric cancer.

Lei-Lei Guo, Chun-Hua Song, Peng Wang … (2015)

Recent studies have showed that RNAs regulate each other with microRNA (miRNA) response elements (MREs) and this mechanism is known as "competing endogenous RNA (ceRNA)" hypothesis. Long non-coding RNAs (lncRNAs) are supposed to play important roles in cancer. Compelling evidence suggests that lncRNAs can interact with miRNAs and regulate the expression of miRNAs as ceRNAs. Several lncRNAs such as H19, HOTAIR and MEG3 have been found to be associated with miRNAs in gastric cancer (GC), generating regulatory crosstalk across the transcriptome. These MRE sharing elements implicated in the ceRNA networks (ceRNETs) are able to regulate mRNA expression. The ceRNA regulatory networks including mRNAs, miRNAs, lncRNAs and circular RNAs may play critical roles in tumorigenesis, and the perturbations of ceRNETs may contribute to the pathogenesis of GC.

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Regulation of laryngeal squamous cell cancer progression by the lncRNA H19/miR-148a-3p/DNMT1 axis

Tianyi Wu, Lingmei Qu, Guoqing He … (2016)

Laryngeal squamous cell carcinoma (LSCC) is a highly aggressive malignant cancer. The regulation of LSCC progression by long non-coding RNA (lncRNA) was not well understood. In this study, we reported that the lncRNA H19 was upregulated in LSCC. The expression levels of H19 were inversely correlated with the survival rate of LSCC patients. Knockdown of H19 expression inhibited LSCC cell migration, invasion and proliferation. We identified microRNA miR-148a-3p as an inhibitory target for H19. Overexpression of miR-148a-3p reduced LSCC migration, invasion and proliferation cell, while inhibition of miR-148a-3p did the opposite. The inhibition of LSCC progression induced by H19 knockdown required the activity of miR-148a-3p. We also identified DNA methyltransferase enzyme DNMT1 as a target of miR-148a-3p. Cellular DNA methylation levels were inhibited by both miR-148a-3p overexpression and H19 knockdown. In summary, our study demonstrated that the lncRNA H19 promoted LSCC progression via miR-148a-3p and DNMT1.