Overexpression of long non-coding RNA MFI2 promotes cell proliferation and suppresses apoptosis in human osteosarcoma

  • Authors:
    • Zhixun Yin
    • Hongmei Ding
    • Erming He
    • Jingmhen Chen
    • Ming Li
  • View Affiliations

  • Published online on: August 11, 2016     https://doi.org/10.3892/or.2016.5013
  • Pages: 2033-2040
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Abstract

The long non-coding RNA MFI2 antisense RNA is overexpressed in human cancer tissues and its increased expression is associated with occurrence and metastasis of cancer. However, the underlying mechanism in evolution and progression of human osteosarcoma is not well known. In the present study, we aimed to evaluate the molecular mechanism of lncRNA MFI2 in promoting osteosarcoma cell proliferation and suppressing apoptosis. We found that the lncRNA MFI2 was significantly overexpressed in human osteosarcoma tissues. Knockdown of lncRNA MFI2 expression suppressed MG63 and SAOS-2 cell proliferation, migration and invasion, and induced cell apoptosis. Furthermore, the expression of forkhead box P4 (FOXP4) was significantly increased and it was positively associated with lncRNA MFI2 expression in tumor tissues. In addition, knockdown of FOXP4 expression by RNA interference strategy inhibited osteosarcoma cell proliferation, migration and invasion, and promoted cell apoptosis. All the results indicated lncRNA MFI2 could promote proliferation and migration of osteosarcoma cells by regulating FOXP4 expression, which suggested critical roles of lncRNA MFI2 and FOXP4 in occurrence and development of human osteosarcoma.

Introduction

Osteosarcoma is one of the most common human primary bone cancers in children and young adults, which mainly presents around the active bone growth and reparation regions, and accounts for nearly 15% of all bone cancers (1). In the recent 25 years, the incidence of osteosarcoma increased 1.4% per year (2). Osteosarcoma is not only locally destructive, but it also has a high metastatic potential (3). At present, the standard treatment is surgical operation and neoadjuvant chemotherapy. For the last 30 years, the therapy has effectively improved patients survival rate, but poor prognosis still threaten the patients with recurrent or metastatic osteosarcomas (4,5). Therefore, the standard treatment is not only a critical therapy for improving the prognosis of osteosarcoma patients, but it is also important to prevent the pulmonary metastases during the early stage of the tumor. However, this cancer is difficult to diagnose and confirm at the initial stage. The limitations of established osteosarcoma biomarkers require us to identify better molecular target that could be clinically useful for diagnosis and prognosis, in particular, for the high-risk patient groups with high risk of progression, recurrence and metastasis.

As is known, only less than 2% of the genome serves as the transcription template for protein coding, whereas more than 70% of the human genes transcripted into non-coding RNAs (6). The non-coding transcripts are named as non-coding RNAs (ncRNAs). The non-coding RNAs are classified as small or long non-coding RNAs (lncRNAs) according to length. lncRNAs are a group of RNAs more than 200 nt in length with limited or no protein-coding capacity (7,8). Most lncRNAs are evolutionarily conserved and strictly regulated, playing critical roles in regulating gene expression (9). lncRNAs are often dysregulated and are involved in the occurrence and development of human cancers (10,11). Substantial evidence revealed that lncRNAs have tumor suppressor or oncogenic roles in tumorigenesis. It is well known that lncRNA HOTAIR acts as an oncogene involved in tumor pathogenesis. The expression of lncRNA HOTAIR is consistently upregulated and it was identified as a strong prognosis biomarker of patient outcomes, including patient survival and metastasis in various human tumors (1214). lncRNA MALAT1 is an oncogenic lncRNA, which was found overexpressed in several tumor tissues and it controls cell proliferation and cell cycle progression (15,16). lncRNA SNHG12 is an oncogene which is upregulated in human osteosarcoma. Knockdown of SNHG12 suppressed cell growth, invasion and migration (17). Nevertheless, the overall pathophysiological contributions of lncRNAs to osteosarcoma remain unknown. Previous study showed that the expression of lncRNA MFI2 was significantly upregulated in human osteosarcoma (18). However, little is known of the exact role of lncRNA MFI2 in evolution and progression of human osteosarcoma.

In the present study, we first performed quantitative real-time PCR analysis of the expression level of lncRNA MFI2 in human osteosarcoma tissues, and found that the expression of MFI2 was significantly increased in tumor tissues when compared with matched adjacent normal tissues, which is consistent with the result of DNA microarray. However, the role of lncRNA MFI2 in osteosarcoma is poorly known and its functional significance has not yet been established. In the present study, we demonstrated that increased expression of MFI2 was a characteristic molecular change in osteosarcoma. Furthermore, we investigated the effect of knockdown of MFI2 on the proliferation, migration, invasion and apoptosis of osteosarcoma cells in vitro. Our findings suggest that lncRNA MFI2 may represent a novel biomarker in osteosarcoma and may be a potential therapeutic target for diagnosis and therapy.

Materials and methods

Tissue collection

Between 2014 and 2015, 43 osteosarcoma and matched adjacent normal tissues were obtained from patients who underwent surgery at the First Affiliated Hospital of Guangzhou Medical University, and were diagnosed with osteosarcoma (stages II and III) based on histopathological evaluation according to the International Union for Cancer Control (UICC). No local or systemic treatment was conducted in these patients before the operation. All volunteers provided written consent for the use of their specimens in this study. All tissues were collected and immediately frozen in liquid nitrogen, and stored at −80°C until RNA extraction. The present study was approved by the Research Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University.

Cell lines and culture conditions

Human osteoblasts cell line hFOB (OB3) and human osteosarcoma cell lines, SAOS-2, MG63, and U-2OS were purchased from the American Type Culture Collection (ATCC) (Manassas, VA, USA). The osteoblasts and osteosarcoma cells were maintained according to the vendor's instructions. In brief, SAOS-2 and U-2OS cells were cultured in McCoy's 5A medium (modified) (ATCC). MG-63 cells were cultured in Eagle's minimum essential medium (EMEM) (ATCC). Human osteosarcoma cells were all cultured with 10% fetal bovine serum (FBS). hFOB (OB3) cells were cultured in a 1:1 mixture of Ham's F12 medium Dulbecco's modified Eagle's medium, with 2.5 mM L-glutamine and 20% FBS. All medium contained 1% penicillin-streptomycin (100 U/ml penicillin and 100 μg/ml streptomycin). All cells were cultured and maintained in a humidified incubator at 37°C and supplemented with 5% CO2.

RNA extraction and quantitative real-time PCR (qRT-PCR) analysis

Total RNA was extracted using TRIzol reagent (Invitrogen Inc., Carlsbad, CA, USA). For qRT-PCR, 2 μg of total RNA was used for reverse transcription reaction and cDNA synthesis using M-MLV reverse transcriptase (Promega, Madison, WI, USA). Quantitative real-time PCR analyses were performed with SYBR-Green Real-Time Master Mix (Toyobo, Tokyo, Japan). Results were normalized to a constitutive expression gene, GAPDH. The PCR primers for MIF2 were: 5′-CACTGCTGAGACGACATCCCTT-3′ (forward) and 5′-GACTTGCTCTTTGGGTCACTGTAT-3′ (reverse); for FOXP4, 5′-GCCATCCTGGAAACCCCT-3′ (forward) and 5′-CTGATACTCCCGCTCGTC-3′ (reverse); for GAPDH, 5′-TGTTCGTCATGGGTGTGAA-3′ (forward) and 5′-ATGGCATGGACTGTGGTCAT-3′ (reverse). qRT-PCR and data collection were performed on Applied Biosystems 7500 Sequence Detection system (ABI, USA). The relative expression levels of MFI2 and FOXP4 were calculated and normalized using the 2−ΔΔCt method.

Protein extraction and western blotting

Total proteins were extracted using SDS lysis buffer (Beyotime, Jiangsu, China) on ice for 30 min and the protein concentration were determined using BCA protein assay kit (Pierce, Rockford, IL, USA). Equal amounts of total proteins were separated by 12% SDS-polyacrylamide gel electrophoresis (SDS-PAGE), transferred to 0.22 μm polyvinylidene fluoride (PVDF) membranes (Millipore, Billerica, MA, USA) and incubated with FOXP4 (1:1,000) or GAPDH (1:1,500) antibodies (both from Abcam, Cambridge, MA, USA). Proteins were detected by enhanced chemiluminescence (ECL) as described by the manufacturer (Beyotime), and the intensity of the bands was quantified by densitometry (Quantity One software; Bio-Rad, Hercules, CA, USA).

siRNA transfection

The small interfering RNA (siRNA) targeting MFI2 (5′-AAAUUGUUUAGGUUUGUGGGG-3′ and 5′-CCACAAACCUAAACAAUUUCG-3′); FOXP4 (5′-UGUAGAACUCAUGAUUCUGGG-3′ and 5′-CAGAAUCAUGAGUUCUACAAG-3′); scrambled sequence negative control (5′-UCUUCCGAACGUGUCACGUTT-3′ and 5′-ACRUGACACGUUCGGAGAATT-3′) were obtained from GenePharma (Shanghai, China). Osteosarcoma cells were seeded into 24-well plates (1×105/well) for 24 h. Then, cells were transfected with MFI2-siRNA or FOXP4-siRNA or scrambled sequence (NC) (100 nM) using Lipofectamine 2000 (Invitrogen) in serum-free medium in accordance with the manufacturer's instructions.

Cell viability assay

The cell viability of osteosarcoma cells with siRNA duplexes at 24, 48 and 72 h was detected using Cell Counting Kit-8 (CCK-8) (Dojindo, Kumamoto, Japan) according to the manufacturer's instructions. In brief, 1×104 cells/well were seeded into 96-well tissue culture plates for 24, 48 and 72 h. Then, osteosarcoma cells were treated with CCK-8 at 37°C for 1 h. Osteosarcoma cells was used to measure the absorbency at 450 nm using a microplate reader Thermo Plate (Rayto Life and Analytical Sciences Co., Ltd., Germany).

Flow cytometry

Cell apoptosis was detected using Annexin V-FITC/PI apoptosis detection kit (Life Technologies, Grand Island, NY, USA) by flow cytometry in accordance with the manufacturer's instructions. Briefly, 5×106 cells were harvested and stained using the Annexin V-FITC/PI apoptosis detection kit. Then, samples were analyzed by a FACScan (Becton-Dickinson, San Diego, CA, USA) flow cytometry. Annexin V(+)/P() and Annexin V(+)/P(+) represent the osteosarcoma cells in early apoptosis and late apoptosis/necrosis, respectively.

Cell migration and invasion assays

Transwell migration and Matrigel invasion assays were performed using 24-well Transwell inserts with 8-μm pore size (Corning Costar Corp., Corning, NY, USA), respectively. For Transwell migration assay, 2×104 osteosarcoma cells suspended in 100 μl serum-free corresponding culture medium were loaded into upper chamber of Transwell insert with non-coated membrane. For Transwell invasion assay, 3×104 osteosarcoma cells were plated in 100 μl corresponding culture medium without FBS in the upper Matrigel-coated chamber instead. In both assays, 500 μl of culture medium containing 20% FBS was added to the lower chamber for culture. The cells were cultured in a humidified atmosphere for 24 h at 37°C and 5% CO2, and the non-invading cells were removed. The migrated or invaded cells were fixed with 100% methanol for 30 min and stained using 0.5% crystal violet (Sigma, St. Louis, MO, USA) for 20 min, and the permeating cells were counted under a phase-contrast microscope (Olympus, Tokyo, Japan).

Statistical analysis

The SPSS 20.0 program (SPSS, Inc., Chicago, IL, USA) was used for statistical analyses. For quantitative data, all experiments were performed at least three times. All data are expressed as the mean ± SD. One-way analysis of variance (ANOVA) or a paired Student's t-test was used to statistical analysis. To assess interaction between the variables, the MFI2 expression level was cross-correlated with FOXP4 in the univariate Cox model, and interaction was evaluated by the Wald test. P-value of <0.05 was considered to indicate a statistically significant result.

Results

lncRNA MFI2 is upregulated in human osteosarcoma tissues and osteosarcoma cell lines

To investigate the expression level of MFI2 in human osteosarcoma tissues, qRT-PCR was used to examine MFI2 expression in 43 paired osteosarcoma samples and matched adjacent normal tissues. As shown in Fig. 1A, MFI2 was significantly upregulated in human osteosarcoma tissues compared with corresponding adjacent, histological normal tissues (P<0.0001). In addition, the expression level of MFI2 was also detected in osteosarcoma cell lines. The result showed that MFI2 was significantly upregulated in osteosarcoma cells (Fig. 1B). Based on the above results, osteosarcoma cell lines SAOS-2 and MG63 were selected for the present study.

Knockdown of MFI2 suppresses osteosarcoma cell proliferation

To evaluate the impact of MFI2 on osteosarcoma cell proliferation, MFI2 was knocked down by MFI2-siRNA transfection. MFI2 was significantly decreased in MG63 and SAOS-2 cells after MFI2-siRNA transfection (Fig. 2A). After transfected with MFI2-siRNA, cell proliferation was performed using CCK-8 assay. The results showed osteosarcoma cell proliferation was significantly suppressed by knockdown of MFI2 (Fig. 2B).

Knockdown of MFI2 inhibits osteosarcoma cell migration and invasion in vitro

To assess the role of MFI2 on tumor cell migration and invasion, Transwell assay was used to detect the migration and invasion ability of MG63 and SAOS-2 cells after MFI2-siRNA transfection. Knockdown of MFI2 inhibited the migration and invasion of MG63 and SAOS-2 cells (Fig. 3).

Knockdown of MFI2 promotes osteosarcoma cell apoptosis in vitro

To confirm the effect of MFI2 on cell apoptosis, the Annexin V-FITC/PI staining method was performed to detec T cell apoptosis. The results showed apoptosis rates were increased in MG63 and SAOS-2 cells after MFI2-siRNA transfection (Fig. 4). The apoptosis rates of MG63 cells transfected with NC-siRNA and MFI2-siRNA were 11.6±2.4 and 45.1±6.4%, respectively (Fig. 4). In addition, the apoptosis rates of SAOS-2 cells transfected with NC-siRNA and MFI2-siRNA were 8.6±1.8 and 30.8±5.4%, respectively (Fig. 4).

FOXP4 protein is upregulated in osteosarcoma tissues and positively correlated with MFI2 expression

The expression of FOXP4 protein was analyzed by western blotting. It was observed that FOXP4 protein was significantly upregulated in osteosarcoma tissues, compared with matched normal tissues (Fig. 5A and B). As both the expression of MFI2 and FOXP4 were significantly enhanced, we considered a correlation between MFI2 expression and FOXP4 expression in osteosarcoma. FOXP4 protein expression levels were positively associated with MFI2 expression levels in 43 osteosarcoma tissues (P=0.0021; R=0.2088; Fig. 5C). Knockdown of lncRNA MFI2 expression suppressed the expression of FOXP4 (Fig. 5D).

Knockdown of FOXP4 suppresses osteosarcoma cell proliferation

To detect the role of FOXP4 on osteosarcoma cell proliferation, FOXP4 was knocked down by FOXP4-siRNA transfection. The expression of FOXP4 at mRNA and protein level was significantly decreased in MG63 and SAOS-2 cells after FOXP4-siRNA transfection (Fig. 6A and B). After FOXP4-siRNA transfection, osteosarcoma cell proliferation was significantly suppressed (Fig. 6C).

Knockdown of MFI2 inhibits cell migration and invasion

To confirm the effect of FOXP4 on cell migration and invasion, Transwell assay was used to detect the migration and invasion ability of MG63 and SAOS-2 cells after FOXP4-siRNA transfection. Knockdown of FOXP4 inhibited the migration and invasion ability of MG63 and SAOS-2 cells (Fig. 7).

Knockdown of FOXP4 promotes osteosarcoma cell apoptosis

To evaluate the impact of FOXP4 on cell apoptosis, the apoptosis assay was performed using Annexin V-FITC/PI staining method. The results showed apoptosis rates were increased in osteosarcoma cells after MFI2-siRNA transfection (Fig. 8). The apoptosis rates of MG63 cells transfected with NC-siRNA and MFI2-siRNA were 11.6±1.8 and 39.8±4.5%, respectively (Fig. 8). In addition, the apoptosis rates of SAOS-2 cells transfected with NC-siRNA and MFI2-siRNA were 10.8±1.9 and 36.8±4.8%, respectively (Fig. 8).

Discussion

In recent years, a series of studies found that numerous lncRNAs played important roles in fundamental cellular processes, such as promoting cellular growth and difference and affecting epigenetic information (1921). It is increasingly recognized that the disorder of lncRNA expression involved in major pathologies, such as human cancer, resulting in progressive and uncontrolled tumor growth (2224). Effective cell proliferation and survival intervention plays a critical role in preventing oncogenesis and treating cancer successfully. Therefore, increased understanding of lncRNA biological function may provide potential approaches for the diagnosis and treatment of human osteosarcoma.

In a previous study, the expression long non-coding RNA MFI2 was significantly upregulated in human osteosarcoma tissues (18). However, the exact role of MFI2 in evolution and progression of osteosarcoma is unknown. The present study was designed to investigate the role of MFI2 in occurrence and development of osteosarcoma. Our results showed that the expression of lncRNA MFI2 was significantly increased in osteosarcoma tissues and cell lines. In cellular functional studies, the results of CCK-8, Transwell and flow cytometric assays illustrated that knockdown of MFI2 by RNA interference markedly suppressed cell proliferation, migration and invasion in osteosarcoma cells, and promoted cell apoptosis. Furthermore, the expression of forkhead box P4 (FOXP4) was also detected using western blotting. The results showed FOXP4 was significantly overexpressed in osteosarcoma tissues, and FOXP4 protein expression levels were positively correlated with MFI2 expression levels. Taken together, our findings indicate that MIF2 could act as an oncogene through regulating cell growth, invasion, migration and apoptosis by regulating FOXP4 expression, and may be useful in diagnosis and treatment of osteosarcoma.

Forkhead box family transcription factors play important roles in cell type- and tissue-specific gene transcription regulation (25). FOXP4 as one of the FOXP subfamily members of winged-helix transcription factors, coding a 685-amino acid protein that is similar to FOXP1 and FOXP2 (26). During embryonic development, the expression of FOXP4 is observed pri marily in gut, neural and pulmonary tissues (27). Wiehagen et al found that FOXP4 is expressed in immature thymocytes and mature T lymphocyte subsets and it is dispensable for T cell development. However, FOXP4 is required for normal T cell cytokine robust recall responses (28). In addition, Long et al successfully replicated the association of rs1983891 (FOXP4) with prostate cancer and provide further support for association of the FOXP4 with prostate cancer in Eastern Asian populations (29). Furthermore, the expression of FOXP4 was found increased in human hepatocellular carcinoma (HCC), knockdown of FOXP4 significantly suppressed HCC cell proliferation and colony formation in vitro by causing cell cycle arrest (30). However, the expression of FOXP4 in osteosarcoma tissues and its role in evolution and progression of osteosarcoma are still poorly known. In the present study, our results indicated that FOXP4 expression was significantly increased in osteosarcoma tissues and cell lines. Knockdown of FOXP4 by FOXP4-siRNA transfection markedly suppressed cell proliferation, migration and invasion in osteosarcoma cells, and promoted cell apoptosis. All the results indicate that upregulation of lncRNA MFI2 may promote osteosarcoma cell proliferation through the FOXP4-mediated signal pathway.

In conclusion, we demonstrated that lncRNA MFI2 and FOXP4 protein are upregulated in osteosarcoma tissues and cell lines, and FOXP4 protein expression levels were positively associated with MFI2 expression levels. Knockdown of MFI2 and FOXP4 by RNA interference markedly suppressed cell proliferation, migration and invasion in osteosarcoma cells, and promoted cell apoptosis. Above all, lncRNA MFI2 was able to promote osteosarcoma cell proliferation by accelerating FOXP4, which indicated critical roles of MFI2 and FOXP4 in evolution and progression of osteosarcoma and may lead to new diagnostic and therapeutic approaches for osteosarcoma.

References

1 

Picci P: Osteosarcoma (osteogenic sarcoma). Orphanet J Rare Dis. 2:62007. View Article : Google Scholar : PubMed/NCBI

2 

Caudill JS and Arndt CA: Diagnosis and management of bone malignancy in adolescence. Adolesc Med State Art Rev. 18:62–78. ix2007.

3 

Walkley CR, Qudsi R, Sankaran VG, Perry JA, Gostissa M, Roth SI, Rodda SJ, Snay E, Dunning P, Fahey FH, et al: Conditional mouse osteosarcoma, dependent on p53 loss and potentiated by loss of Rb, mimics the human disease. Genes Dev. 22:1662–1676. 2008. View Article : Google Scholar : PubMed/NCBI

4 

O'Day K and Gorlick R: Novel therapeutic agents for osteosarcoma. Expert Rev Anticancer Ther. 9:511–523. 2009. View Article : Google Scholar : PubMed/NCBI

5 

Bielack SS, Marina N, Ferrari S, Helman LJ, Smeland S, Whelan JS and Reaman GH: Osteosarcoma: The same old drugs or more? J Clin Oncol. 26:3102–3105. 2008. View Article : Google Scholar : PubMed/NCBI

6 

Bertone P, Stolc V, Royce TE, Rozowsky JS, Urban AE, Zhu X, Rinn JL, Tongprasit W, Samanta M, Weissman S, et al: Global identification of human transcribed sequences with genome tiling arrays. Science. 306:2242–2246. 2004. View Article : Google Scholar : PubMed/NCBI

7 

Guttman M, Amit I, Garber M, French C, Lin MF, Feldser D, Huarte M, Zuk O, Carey BW, Cassady JP, et al: Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature. 458:223–227. 2009. View Article : Google Scholar : PubMed/NCBI

8 

Nagano T and Fraser P: No-nonsense functions for long noncoding RNAs. Cell. 145:178–181. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Mercer TR, Dinger ME and Mattick JS: Long non-coding RNAs: Insights into functions. Nat Rev Genet. 10:155–159. 2009. View Article : Google Scholar : PubMed/NCBI

10 

Cheetham SW, Gruhl F, Mattick JS and Dinger ME: Long noncoding RNAs and the genetics of cancer. Br J Cancer. 108:2419–2425. 2013. View Article : Google Scholar : PubMed/NCBI

11 

Yang G, Lu X and Yuan L: LncRNA: A link between RNA and cancer. Biochim Biophys Acta. 1839:1097–1109. 2014. View Article : Google Scholar : PubMed/NCBI

12 

Nie Y, Liu X, Qu S, Song E, Zou H and Gong C: Long non-coding RNA HOTAIR is an independent prognostic marker for nasopharyngeal carcinoma progression and survival. Cancer Sci. 104:458–464. 2013. View Article : Google Scholar : PubMed/NCBI

13 

Niinuma T, Suzuki H, Nojima M, Nosho K, Yamamoto H, Takamaru H, Yamamoto E, Maruyama R, Nobuoka T, Miyazaki Y, et al: Upregulation of miR-196a and HOTAIR drive malignant character in gastrointestinal stromal tumors. Cancer Res. 72:1126–1136. 2012. View Article : Google Scholar : PubMed/NCBI

14 

Li J, Yang S, Su N, Wang Y, Yu J, Qiu H and He X: Erratum to: Overexpression of long non-coding RNA HOTAIR leads to chemoresistance by activating the Wnt/β-catenin pathway in human ovarian cancer. Tumour Biol. 36:9093–9094. 2015. View Article : Google Scholar : PubMed/NCBI

15 

Zhou X, Liu S, Cai G, Kong L, Zhang T, Ren Y, Wu Y, Mei M, Zhang L and Wang X: Long non-coding RNA MALAT1 promotes tumor growth and metastasis by inducing epithelial-mesenchymal transition in oral squamous cell carcinoma. Sci Rep. 5:159722015. View Article : Google Scholar

16 

Tripathi V, Shen Z, Chakraborty A, Giri S, Freier SM, Wu X, Zhang Y, Gorospe M, Prasanth SG, Lal A, et al: Long noncoding RNA MALAT1 controls cell cycle progression by regulating the expression of oncogenic transcription factor B-MYB. PLoS Genet. 9:e10033682013. View Article : Google Scholar : PubMed/NCBI

17 

Ruan W, Wang P, Feng S, Xue Y and Li Y: Long non-coding RNA small nucleolar RNA host gene 12 (SNHG12) promotes cell proliferation and migration by upregulating angiomotin gene expression in human osteosarcoma cells. Tumour Biol. 37:4065–4073. 2016. View Article : Google Scholar

18 

Li JP, Liu LH, Li J, Chen Y, Jiang XW, Ouyang YR, Liu YQ, Zhong H, Li H and Xiao T: Microarray expression profile of long noncoding RNAs in human osteosarcoma. Biochem Biophys Res Commun. 433:200–206. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Kotake Y, Nakagawa T, Kitagawa K, Suzuki S, Liu N, Kitagawa M and Xiong Y: Long non-coding RNA ANRIL is required for the PRC2 recruitment to and silencing of p15INK4B tumor suppressor gene. Oncogene. 30:1956–1962. 2011. View Article : Google Scholar

20 

Liu Y, Zhao J, Zhang W, Gan J, Hu C, Huang G and Zhang Y: lncRNA GAS5 enhances G1 cell cycle arrest via binding to YBX1 to regulate p21 expression in stomach cancer. Sci Rep. 5:101592016. View Article : Google Scholar

21 

Su L, Han D, Wu J and Huo X: Skp2 regulates non-small cell lung cancer cell growth by Meg3 and miR-3163. Tumour Biol. 37:3925–393. 2015. View Article : Google Scholar : PubMed/NCBI

22 

Hrdlickova B, de Almeida RC, Borek Z and Withoff S: Genetic variation in the non-coding genome: Involvement of micro-RNAs and long non-coding RNAs in disease. Biochim Biophys Acta. 1842:1910–1922. 2014. View Article : Google Scholar : PubMed/NCBI

23 

Kung JT, Colognori D and Lee JT: Long noncoding RNAs: Past, present, and future. Genetics. 193:651–669. 2013. View Article : Google Scholar : PubMed/NCBI

24 

Morris KV and Mattick JS: The rise of regulatory RNA. Nat Rev Genet. 15:423–437. 2014. View Article : Google Scholar : PubMed/NCBI

25 

Chokas AL, Trivedi CM, Lu MM, Tucker PW, Li S, Epstein JA and Morrisey EE: Foxp1/2/4-NuRD interactions regulate gene expression and epithelial injury response in the lung via regulation of interleukin-6. J Biol Chem. 285:13304–13313. 2010. View Article : Google Scholar : PubMed/NCBI

26 

Teufel A, Wong EA, Mukhopadhyay M, Malik N and Westphal H: FoxP4, a novel forkhead transcription factor. Biochim Biophys Acta. 1627:147–152. 2003. View Article : Google Scholar : PubMed/NCBI

27 

Lu MM, Li S, Yang H and Morrisey EE: Foxp4: A novel member of the Foxp subfamily of winged-helix genes co-expressed with Foxp1 and Foxp2 in pulmonary and gut tissues. Gene Expr Patterns. 2:223–228. 2002. View Article : Google Scholar

28 

Wiehagen KR, Corbo-Rodgers E, Li S, Staub ES, Hunter CA, Morrisey EE and Maltzman JS: Foxp4 is dispensable for T cell development, but required for robust recall responses. PLoS One. 7:e422732012. View Article : Google Scholar : PubMed/NCBI

29 

Long QZ, Du YF, Ding XY, Li X, Song WB, Yang Y, Zhang P, Zhou JP and Liu XG: Replication and fine mapping for association of the C2orf43, FOXP4, GPRC6A and RFX6 genes with prostate cancer in the Chinese population. PLoS One. 7:e378662012. View Article : Google Scholar : PubMed/NCBI

30 

Wang G and Sun Y, He Y, Ji C, Hu B and Sun Y: MicroRNA-338-3p inhibits cell proliferation in hepatocellular carcinoma by target forkhead box P4 (FOXP4). Int J Clin Exp Pathol. 8:337–344. 2015.PubMed/NCBI

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October-2016
Volume 36 Issue 4

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Spandidos Publications style
Yin Z, Ding H, He E, Chen J and Li M: Overexpression of long non-coding RNA MFI2 promotes cell proliferation and suppresses apoptosis in human osteosarcoma. Oncol Rep 36: 2033-2040, 2016
APA
Yin, Z., Ding, H., He, E., Chen, J., & Li, M. (2016). Overexpression of long non-coding RNA MFI2 promotes cell proliferation and suppresses apoptosis in human osteosarcoma. Oncology Reports, 36, 2033-2040. https://doi.org/10.3892/or.2016.5013
MLA
Yin, Z., Ding, H., He, E., Chen, J., Li, M."Overexpression of long non-coding RNA MFI2 promotes cell proliferation and suppresses apoptosis in human osteosarcoma". Oncology Reports 36.4 (2016): 2033-2040.
Chicago
Yin, Z., Ding, H., He, E., Chen, J., Li, M."Overexpression of long non-coding RNA MFI2 promotes cell proliferation and suppresses apoptosis in human osteosarcoma". Oncology Reports 36, no. 4 (2016): 2033-2040. https://doi.org/10.3892/or.2016.5013