Long noncoding RNA FER1L4 suppresses cancer cell growth by acting as a competing endogenous RNA and regulating PTEN expression

Xia, Tian; Chen, Shengcan; Jiang, Zhen; Shao, Yongfu; Jiang, Xiaoming; Li, Peifei; Xiao, Bingxiu; Guo, Junming

doi:10.1038/srep13445

Cited by 135 publications

(100 citation statements)

References 66 publications

(95 reference statements)

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“…FER1L4, a novel long non-coding RNA, has been reported to be involved in initiation and development of multiple cancers by regulating cancer cell proliferation, migration, apoptosis, and invasion [11][12][13][14][15]. For example, Wu et al reported that FER1L4 could exert a tumor suppressive effect on liver cancer, at least partially, through suppression of miR-106a-5p expression [13].…”

Section: Discussionmentioning

confidence: 99%

“…Fer-1-like protein 4 (FER1L4), a newly identified tumor-associated lncRNA, has been reported to be downregulated in gastric cancer [11,12], hepatocellular carcinoma [13], colon cancer [14], and endometrial carcinoma [15], and acts as a tumor suppressor in these cancers. However, the clinical significance and biological role of FER1L4 in OS is still unclear.…”

Section: Introductionmentioning

confidence: 99%

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Long Noncoding RNA FER1L4 Suppresses Tumorigenesis by Regulating the Expression of PTEN Targeting miR-18a-5p in Osteosarcoma

Fei

Zhang

Liu

et al. 2018

Cell Physiol Biochem

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Background/Aims: Novel long non-coding RNA Fer-1-like protein 4 (FER1L4) has been reported to play crucial regulatory roles in tumor progression. However, its clinical significance and biological role in osteosarcoma (OS) is completely unknown. The aim of the present study was to investigate the role of FER1L4 in OS progression and the underlying mechanism. Methods: We analyzed the expression levels of FER1L4 in tissues of OS patients and cell lines via quantitative RT-PCR (qRT-PCR). The effect of FER1L4 on cell proliferation, colony formation, migration and invasion was analyzed by cell counting kit-8 (CCK-8), colony formation, wound healing and transwell invasion assay, respectively. Novel targets of FER1L4 were selected through a bioinformatics soft and confirmed using a dual-luciferase reporter system and qRT-PCR. To detect the role of FER1L4 in vivo tumorigenesis, tumor xenografts were created. Results: We found that the expression of FER1L4 was significantly downregulated in OS tissues and cell lines; moreover, low expression of FER1L4 was associated with advanced tumor-nude-metastasis (TNM) stage, lymph node metastases, and poor overall survival. Functional assays showed that upregulation of FER1L4 significantly inhibited OS cell proliferation, colony formation, migration, and invasion in vitro, as well as suppressed tumor growth in vivo. Assays performed to determine the underlying mechanism, indicated that FER1L4 interacted directly with miR-18a-5p. Subsequently, we found that FER1L4 significantly increased PTEN expression, a known target of miR-18a-5p, in OS cells. Furthermore, PTEN was found to be down-regulated, and positively correlated with FER1L4 in OS tissues. Conclusion: These findings suggest that FER1L4, acting as a competing endogenous RNA (ceRNA) of miR-18a-5p, exerts its anti-cancer role by modulating the expression of PTEN. Thus, FER1L4 may be a novel target for the prevention and treatment of OS.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Long Noncoding RNA FER1L4 Suppresses Tumorigenesis by Regulating the Expression of PTEN Targeting miR-18a-5p in Osteosarcoma

Fei

Zhang

Liu

et al. 2018

Cell Physiol Biochem

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“…14 Interestingly, lncRNAs can act as competing endogenous RNAs (ceRNAs) to sponge miRNAs, consequently modulating the derepression of miRNA targets. 31 For instance, Xia et al 32 found that lncRNA fer-1-like family member 4 (FER1L4) acts as a ceRNA to regulate the expression of PTEN by taking up miR-106a-5p in gastric cancer. As confirmed by situ hybridization assay, HOTAIR was distributed in both nucleus and cytoplasm 33 , and has been reported to be able to bind miRNAs in cancers.…”

Section: Discussionmentioning

confidence: 99%

HOTAIR Epigenetically Modulates PTEN Expression via MicroRNA-29b: A Novel Mechanism in Regulation of Liver Fibrosis

et al. 2017

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“…Complementary DNA was subsequently generated using the GoScript™ Reverse Transcription system (Promega Corporation, Madison, WI, USA), following the manufacturer's protocol, as previously reported (14). In order to detect plasma GACAT2 levels, RT-qPCR was performed with GoTaq qPCR Master mix (Promega Corporation) on a Mx3005P qPCR system (Stratagene; Agilent Technologies, Inc., Santa Clara, CA, USA) following the manufacturer's protocol.…”

Section: Rna Extraction and Reverse Transcription-quantitative Polymementioning

confidence: 99%

Plasma lncRNA-GACAT2 is a valuable marker for the screening of gastric cancer

et al. 2016

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Abstract. Long non-coding RNAs (lncRNAs) are crucial in contributing to gastric tumorigenesis and development. However, the diagnostic value of the majority of lncRNAs in gastric cancer (GC) are not clear. The present study investigated the diagnostic value of gastric cancer associated transcript 2 (GACAT2), a lncRNA that is aberrantly expressed in GC tissues. A total of 343 plasma samples from 80 healthy individuals, 29 patients with gastric dysplasia (GD) and 117 paired preoperative and postoperative patients with GC were collected. Plasma GACAT2 levels were subsequently measured by reverse transcription-quantitative polymerase chain reaction. Finally, the associations between plasma GACAT2 levels and various clinicopathological features of patients with GC were assessed. The results demonstrated that plasma GACAT2 levels in preoperative patients with GC were significantly higher than those in the postoperative group (P=0.031). Compared with healthy individuals, plasma GACAT2 levels were significantly increased in patients with GD (P<0.001) and preoperative patients with GC (P=0.040). Moreover, the individual relative changes of plasma GACAT2 expression following surgery were significantly associated with lymphatic metastasis (P=0.034), distal metastasis (P=0.035) and perineural invasion (P=0.039). Therefore, the results of the current study suggest that plasma-based GACAT2 may be developed as a tumor marker to screen and predict the prognosis of GC patients. IntroductionGastric cancer (GC) is one of the most prevalent malignant tumors (1). A number of cancer prevention studies have demonstrated that the most effective way to reduce GC-associated mortality is through early diagnosis and appropriate treatment (2-4). However, the diagnosis rate of early GC remains extremely low (<10%) (5). Patients with GC are usually diagnosed following identification of tumors on B-mode ultrasound, computerized tomography, or magnetic resonance imaging scans. However, early GC tumors are often not large enough to be detected by conventional imaging techniques. Furthermore, the sensitivity and specificity of traditional tumor markers are not satisfactory (6). Thus, investigations into new, more efficient tumor markers are important to improve early diagnosis of this disease.Long non-coding RNAs (lncRNAs) are a class of regulatory non-coding RNAs (7). Previous studies have investigated the roles of lncRNAs in tumorigenesis and cancer development. For example, Zang et al (8) reported that lncRNA-PEG10 expression was upregulated in esophageal cancer tissues, and that it regulated the proliferation and invasion of cancer cells. Furthermore, Shao et al (9) demonstrated that lncRNA-AA174084 expression was downregulated in gastric cancer tissues. A previous study determined that gastric cancer associated transcript 2 (GACAT2) was not only significantly downregulated in gastric cancer tissue, but was also aberrantly expressed in gastric precancerous lesions and gastric cell lines (10).Blood is one of the most commonly used samples in ...

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Long noncoding RNA FER1L4 suppresses cancer cell growth by acting as a competing endogenous RNA and regulating PTEN expression

Cited by 135 publications

References 66 publications

Long Noncoding RNA FER1L4 Suppresses Tumorigenesis by Regulating the Expression of PTEN Targeting miR-18a-5p in Osteosarcoma

Long Noncoding RNA FER1L4 Suppresses Tumorigenesis by Regulating the Expression of PTEN Targeting miR-18a-5p in Osteosarcoma

HOTAIR Epigenetically Modulates PTEN Expression via MicroRNA-29b: A Novel Mechanism in Regulation of Liver Fibrosis

Plasma lncRNA-GACAT2 is a valuable marker for the screening of gastric cancer

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