==== Front Biomed Res Int Biomed Res Int BMRI BioMed Research International 2314-6133 2314-6141 Hindawi 10.1155/2020/4157606 Research Article Long Noncoding RNA MALAT1 Promotes Colorectal Cancer Progression by Acting as a ceRNA of miR-508-5p to Regulate RAB14 Expression https://orcid.org/0000-0003-4776-0165Zhang Chen chenzhang0803cz@163.com 1 Yao Kunhou 2 Zhang Junjie 2 Wang Chenyu 2 Wang Chaoyang 2 https://orcid.org/0000-0001-8924-9061Qin Changjiang cjqriver@163.com 2 1First Department of Oncology, Xinxiang Central Hospital, Xinxiang, 453000 Henan, China 2Department of General Surgery, Huaihe Hospital of Henan University, Kaifeng, 475000 Henan, China Academic Editor: Guangcun Huang 2020 4 12 2020 2020 415760618 1 2020 1 5 2020 9 6 2020 Copyright © 2020 Chen Zhang et al.2020This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Accumulating evidence suggested that lncRNA MALAT1 plays critical roles in the commencement and progression of malignant cancers. Nevertheless, the function of MALAT1 in colorectal cancer (CRC) remains largely unknown. In the present study, we reported that MALAT1 expression is significantly upregulated in CRC and correlated with advanced TNM stage, lymph node metastasis, and worse prognosis in patients. Functional assays revealed that MALAT1 knockdown reduced CRC cell growth and invasion abilities in vitro. Mechanistically, we discovered that MALAT1 may serve as a competing endogenous RNA (ceRNA) to miR-508-5p in CRC progression. Bioinformatics analysis and luciferase assays confirmed that RAB14 acts as a target of miR-508-5p. In addition, downregulation of RAB14 reduced the progression of CRC. Collectively, our findings indicated that MALAT1 could promote CRC progress by sponging miR-508-5p and enhancing RAB14 expression, which provides a therapeutic target in CRC treatment. Henan Science and Technology Project182102310372 ==== Body 1. Introduction Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide [1, 2]. Although the prognosis has ameliorated due to advances in both diagnosis and treatment of CRC, the molecular mechanisms that lead to the development of the tumor remain unclear [3, 4]. Therefore, identification of molecular mechanisms underlying CRC progression is of utmost importance in order to find novel therapy targets for CRC patients. Long noncoding RNAs (lncRNAs) are a type of ncRNA with more than 200 nucleotides (nt) with limited protein-coding ability [5]. Recently, accumulating data indicated that aberrant lncRNA expression has important functions in diverse biological processes, including growth, differentiation, autophagy, and metastasis [6, 7]. For example, Zhu et al. [8] demonstrated that lncRNA ANCR decreased osteoblast differentiation by regulating the EZH2/Runx2 axis. Xiong et al. [9] revealed that lncRNA HULC triggered autophagy and chemosensitivity in liver cancer by regulating the expression of Sirt1. Sun et al. [10] demonstrated that lncRNA HOXA11-AS encouraged gastric cancer cell growth and invasion by regulating DNMT1, LSD1, and PRC2 expression. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is first demonstrated by Ji and colleagues as an oncogene in non-small-cell lung cancer through the promotion of cell metastasis and invasion [11]. Recently, dysregulation of MALAT1 was discovered among many other cancers. For example, Zhang et al. [12] indicated that MALAT1 overexpression is connected with advanced clinical features and a worse overall survival rate in renal cell carcinoma. Wu et al. [13] discovered that MALAT1 encourages gallbladder cancer cell proliferation and invasion by regulating the ERK/MAPK axis. Xie et al. [14] demonstrated that MALAT1 increases bladder cancer cell invasion ability by regulating miR-125b expression. Nevertheless, the mechanism of MALAT1 in CRC advancement is still uncertain. 2. Materials and Methods 2.1. Tissue Specimens and Ethics Statement The study was granted approval by the Ethics Committee of Xinxiang Central Hospital and Huaihe Hospital, and all participants granted their informed consent. A total of 43 paired (24 males and 19 females; 51.3 ± 13.81 and 58.7 ± 8.97 years old) tissue samples were gathered from patients who were diagnosed with CRC between Jan 1, 2015, and Dec 1, 2016. No participants were administered radiotherapy or chemotherapy before the operation. All tissue samples were kept at −80°C until use (Table 1). 2.2. Cell Culture and Transfection Human CRC (SW480, HT-29, SW620, LoVo, HCT-8) and normal colon epithelial cell line (FHC) were acquired from American Type Culture Collection (ATCC, Manassas, VA, USA). Cells were grown in Dulbecco's modified Eagle's medium (DMEM; Invitrogen, Carlsbad, CA, USA) accompanied by 10% fetal bovine serum (FBS) and placed at 37°C in 5% CO2. MALAT1 cDNA was cloned into pcDNA3.1 (Invitrogen) to construct a vector that would lead to overexpression of MALAT1 (pcDNA3.1/MALAT1) according to a previous study [15]. The miR-508-5p mimics, MALAT1 siRNA (si-MALAT1-1 sequence is 5′-CACAGGGAAAGCGAGTGGTTGGTAA-3′, si-MALAT1-2 sequence is 5′-GAGGUGUAAAGGGAUUUAUTT3′, and si-MALAT1-3 sequence is 5′-CACAGGGAAAGCGAGUGGUUGGU-3′), RAB14 siRNA, and scramble negative controls were ordered from GenePharma (Shanghai, China). Cells were seeded in 6-well plates (5 × 104 cells/well) and incubated for 24 h before being transfected with the above-mentioned oligonucleotides and plasmids (30 nM) using Lipofectamine 2000 (Invitrogen, Carlsbad, CA, USA) according to the manufacturer's instructions. 2.3. Quantitative Real-Time RT-PCR Total RNA was isolated using a TRIzol reagent (Invitrogen). RNA was reverse transcribed to cDNA by utilizing a reverse transcription kit (TaKaRa, China). The PrimeScript™ RT Reagent Kit (TaKaRa, China) was utilized to identify mRNA expression. U6 or GAPDH served as an endogenous control. The relative fold expression was measured by utilizing the 2-ΔΔCt method. Primer sequences were as follows: MALAT1, 5′-AAAGCAAGGTCTCCCCACAA-3′ (forward) and 5′-GGTCTGTGCTAGATCAAAAGGCA-3′ (reverse); miR-508-5p, 5′-ACACTCCAGCTGGGTACTCCAGAGGGCGTCACT-3′ (forward) and 5′-TGGTGTCGTGGAGTCG-3′ (reverse); and RAB14, 5′-GCAGATTTGGGATACAGCAGGG-3′ (forward) and 5′-CAGTGTTTGGATTGGTGAGATTCC-3′. 2.4. Western Blot The procedure was carried out as previously described (13). Briefly, cells or tissues were lysed, and protein concentrations were measured using the BCA Protein Assay Kit (Pierce, Rockford, IL, USA). Protein samples were resolved by SDS-polyacrylamide gel electrophoresis and transferred to nitrocellulose membranes. The membranes were incubated with anti-RAB14 (1 : 1000, ab28639, Abcam, CA, USA) and anti-GAPDH (1 : 5000, ab181602, Abcam, CA, USA). After washing, the membranes were then incubated with secondary antibodies coupled to horseradish peroxidase for 1 h at room temperature. Protein signals were detected by the Western Lightning Plus ECL kit (PerkinElmer, Waltham, MA, USA) and quantified by densitometry. 2.5. Luciferase Reporter Assay Wild-type or mutant MALAT1 (MALAT1-WT or MALAT1-MUT) and 3′UTR of RAB14 ligated to pGL3-basic vector (Promega, Madison, WI, USA) were used to build pGL3-MALAT1-WT, pGL3-MALAT1-MUT, pGL3-RAB14-WT, and pGL3-RAB14-MUT. Then, these plasmid vectors were cotransfected with miR-508-5p mimics into HEK293T cells. After 48 h of transfection, cells were harvested for the luciferase reporter assay with a Dual-Luciferase Reporter Assay System (Promega). Renilla luciferase was used as an internal reference. 2.6. CCK-8 Assay Cell Counting Kit-8 (CCK-8, Dojindo, Japan) was used to detect cell proliferation. Briefly, transfected cells were added onto 96-well plates (5 × 103 cells/well). Then, 10 μl CCK-8 reagents were placed into every well at 24, 48, and 72 h, respectively. Finally, the optical density (OD) was quantified at 450 nm through a microplate reader (BioTek, VT, USA). 2.7. Colony Formation Assay Six-well plates with transfected cells (2000 cells/well) were maintained for 2 weeks. Then, the colonies were fixed with 4% paraformaldehyde for 30 min and stained with 0.1% crystal violet for 10 min. The clones were imaged by using a microscope (Nikon, Japan). 2.8. Transwell Invasion Assay An invasion assay was carried out by utilizing transwell chamber inserts (24 wells, 8 μm pore size, Corning, NY, USA) which were precoated with Matrigel (BD Biosciences, San Jose, CA, USA), and transfected cells (2 × 104 cells/well) were added to the upper chamber. Added to the lower chamber was 500 μl DMEM containing 15% FBS. Cells in the upper chamber were removed after incubation for 24 h, and cells that invaded the lower membrane surface were fixed with 4% paraformaldehyde and stained with 0.1% crystal violet solution [12]. 2.9. RNA Immunoprecipitation (RIP) Assay According to the manufacturer's protocol, the Magna RIP™ RNA-Binding Protein Immunoprecipitation Kit (Millipore, MA, USA) was applied to conduct the RIP assay by using Ago2 antibody (Abcam) or IgG antibody (negative control). And the immune-precipitated RNAs were finally confirmed using qRT-PCR. 2.10. Statistical Analysis Results from a minimum of 3 independent experiments were statistically analyzed by utilizing SPSS 19.0. Data was expressed as the mean ± standard deviation (SD). The data were analyzed either by two-tailed unpaired Student's t-test (two groups) or by one-way ANOVA (greater than two groups). p values ≤ 0.05 were regarded as statistically significant. 3. Results 3.1. lncRNA MALAT1 Is Highly Expressed in CRC In order to discover the function of MALAT1 in CRC tumorigenesis, analysis of the GEPIA database was performed. Data indicated that MALAT1 was significantly upregulated in colon adenocarcinoma (COAD) in comparison with normal samples. Similarly, MALAT1 was also higher in rectum adenocarcinoma (READ) (Figures 1(a) and 1(b)). High MALAT1 was significantly correlated with an advanced tumor stage in CRC patients (Figure 1(c)). GEPIA analysis showed that patients with high MALAT1 levels were associated with a poor overall survival (OS) rate (Figure 1(d)). Moreover, high MALAT1 levels were significantly associated with the disease-free survival (DFS) rate in CRC patients (Figure 1(e)). We further investigated MALAT1 levels in CRC tissues. qRT-PCR results demonstrated that MALAT1 expression was substantially increased in CRC tissues (Figures 2(a) and 2(b)). High MALAT1 levels were associated with an advanced TNM stage and lymph node metastasis in CRC patients (Figures 2(c) and 2(d)). In addition, MALAT1 expression was significantly upregulated in CRC cell lines (SW480, HT-29, SW620, LoVo, and HCT-8) compared to the normal colon epithelial cell line (FHC) (Figure 2(e)). 3.2. Knockdown of MALAT1 Suppressed CRC Cell Proliferation and Invasion To investigate the biological consequences of MALAT1 in CRC, we suppressed MALAT1 expression in SW480 and HCT-8 cells (Figure 3(a)). CCK-8 and colony formation experiments demonstrated that MALAT1 inhibition substantially decreased SW480 and HCT-8 cell proliferation abilities in vitro (Figures 3(b) and 3(c)). The transwell assay reported that MALAT1 knockdown inhibited SW480 and HCT-8 cell invasion abilities in vitro (Figure 3(d)). 3.3. MALAT1 Binds Directly to miR-508-5p to Facilitate CRC Progression Next, we explored miR-508-5p levels in CRC. qRT-PCR results demonstrated that miR-508-5p levels were significantly reduced in and correlated with advanced TNM stage and lymph node metastasis in CRC patients (Figures 4(a)–4(c)). Kaplan-Meier analysis demonstrated that CRC patients with low miR-508-5p expression had a poor overall survival compared to patients with high miR-508-5p expression (Figure 4(d)). Recent evidence shows that certain lncRNAs sponge the biological functions of miRNAs by acting as competing endogenous RNAs (ceRNAs) [15]. DIANA online software suggested the existence of miR-508-5p binding sites in MALAT1 (Figure 5(a)). The luciferase reporter assay identified that miR-508-5p mimics significantly decreased the luciferase activity of the MALAT1-WT vector (Figure 5(b)). qRT-PCR showed that si-MALAT1 increased miR-508-5p expression in SW480 and HCT-8 cells (Figure 5(c)). The RIP assay further confirmed the correlation between MALAT1 and miR-508-5p in CRC (Figure 5(d)). Spearman's correlation analysis indicated that MALAT1 expression was inversely correlated with miR-508-5p in CRC tissues (Figure 5(e)). Furthermore, rescue assays indicated that MALAT1 overexpression on HCT-8 cell proliferation and invasion could be hindered by miR-508-5p mimics (Figures 5(f) and 5(g)). 3.4. MALAT1 Encourages CRC Progression by Targeting the miR-508-5p/RAB14 Axis Previous studies indicate that miRNAs can bind the 3′UTR of target genes to control their expression [16]. In the present study, we identified RAB14 as a target of miR-508-5p by TargetScan (Figure 6(a)). The luciferase reporter assay indicated that miR-508-5p mimics decreased the luciferase activity of the RAB14-WT group (Figure 6(b)). Western blot indicated that miR-508-5p mimics decreased RAB14 levels in CRC cells (Figures 6(c) and 6(d)). Furthermore, we showed that MALAT1 overexpression increased RAB14 expression in CRC cells, while miR-508-5p mimics abolished the effects (Figures 6(e) and 6(f)). Next, we investigated the roles of RAB14 in CRC progression. GEPIA analysis [17] demonstrated that RAB14 levels were significantly upregulated in CRC (Figures 7(a) and 7(b)). And the results were further validated in 43 pairs of CRC tissues (Figure 7(c)). IHC demonstrated that RAB14 was considerably higher in CRC and associated with metastasis (Figure 7(d)). Kaplan-Meier analysis showed that high RAB14 levels were correlated with a poor disease-free survival rate in CRC patients (Figure 7(e)). Furthermore, the transwell assay indicated that RAB14 inhibition substantially reduced SW480 cell invasion ability in vitro (Figure 7(f)). Thus, these data indicated that MALAT1 could promote CRC progression by regulating the miR-508-5p/RAB14 axis (Figure 7(g)). 4. Discussion Accumulating data shows that lncRNAs play critical roles in CRC development [18]. For example, Liu et al. [19] identified that lncRNA DANCR expression is highly expressed in CRC and correlated with advanced clinical features and worse overall survival. Wang et al. [20] suggested that lncRNA AB073614 regulates CRC cell growth and metastasis via the PI3K/AKT axis. Han et al. [21] reported that lncRNA CRNDE encourages chemoresistance and proliferation by the miR-181a-5p/Wnt/β-catenin axis in CRC. Recently, a number of studies have shown that MALAT1 might be a biomarker in CRC progression. For example, Yang et al. [22] discovered that MALAT1 promotes CRC growth and invasion by regulating AKAP-9. Ji et al. [23] discovered that resveratrol inhibits CRC cell invasion and metastasis through the Wnt/β-catenin axis. Zhuang et al. [24] demonstrated that MALAT1 encourages CRC cell metastasis by the miR-106b-5p/SLAIN2 axis. In this study, we demonstrated that MALAT1 was amplified and correlated with an advanced TNM stage, lymph node metastasis, and worse prognosis in CRC patients. MALAT1 inhibition reduced CRC cell growth and invasion abilities in vitro. Thus, we suggested that MALAT1 may encourage the progression of CRC malignancy, which is consistent with previous studies. Recent studies showed that certain lncRNAs exert their functions partly by acting as ceRNAs and modulating the expression of miRNA targets. In this study, bioinformatics tools indicated that miR-508-5p serves as a target of MALAT1, which was additionally validated using luciferase reporter and RIP assays. Subsequently, rescue assays demonstrated that miR-508-5p mimics abolished the influence of MALAT1 overexpression on CRC progression. Previous studies showed that miR-508-5p acts as a tumor suppressor in many tumors. For example, Wu et al. [25] discovered that miR-508-5p reduces hepatocellular carcinoma cell progression via regulating MESDC1 levels. Bao et al. [26] demonstrated that miR-508-5p suppresses glioma cell growth by targeting GPNMB. Shang et al. [27] proposed that the miR-508-5p/ABCB1 axis regulates gastric cancer multidrug resistance. Therefore, we suggest that MALAT1 might exert its oncogenic function in CRC progression at least partially by controlling miR-508-5p levels. RAB14 is a small GTPase member of the RAS oncogene family, which contains more than 170 members, and is divided into five subfamilies—RAS, RAB, RHO, ARF, and RAN [28]. Recent studies suggest that RAB14 might act as an important regulator in tumor advancement. For example, Guo et al. [29] indicated that RAB14 promotes gastric cancer cell proliferation by controlling the AKT pathway. Wang et al. [30] proposed that miR-451 hindered lung cancer advancement by targeting RAB14. Moreover, Wang et al. [31] found that miR-490-3p hindered CRC progression by targeting RAB14. In our study, we showed that RAB14 was substantially upregulated and correlated with lymph node metastasis and poor prognosis in CRC patients. Subsequently, RAB14 was identified as a target of miR-508-5p. Moreover, RAB14 levels were significantly increased by MALAT1 overexpression, and the upregulation could be abolished by miR-508-5p mimics. Thus, our study suggested that MALAT1 might serve as a ceRNA to promote RAB14-mediated CRC progression by regulating miR-508-5p expression. In conclusion, this work identified that MALAT1 promotes CRC progression by promoting RAB14 via inhibiting miR-508-5p expression. Thus, MALAT1 might serve as a useful biomarker and therapeutic target in CRC treatment. Acknowledgments This work was supported by the Henan Science and Technology Project (No. 182102310372). Data Availability All data used to support the findings of this study are included within the article. Conflicts of Interest The authors declare that there are no competing interests associated with the manuscript. Authors' Contributions Chen Zhang, Kunhou Yao, and Changjiang Qin conceived and designed the study. Chen Zhang, Junjie Zhang, and Chenyu Wang conducted the in vitro experiments and data analysis. Chaoyang Wang collected tissue samples. All authors read and approved the final manuscript. Figure 1 MALAT1 is dysregulated in CRC. (a, b) GEPIA database demonstrated that MALAT1 levels are upregulated in CRC tissues. (c) High MALAT1 levels were correlated with CRC tumor stage. (d) High MALAT1 was correlated with low overall survival in CRC. (e) High MALAT1 was correlated with poor disease-free survival in CRC. COAD: colon adenocarcinoma; READ: rectum adenocarcinoma; T: tumor tissues; N: normal tissues; ∗p < 0.05. Figure 2 MALAT1 is highly expressed in CRC. (a, b) The MALAT1 levels in CRC tissues were evaluated using qRT-PCR. (c, d) High MALAT1 levels were correlated with advanced TNM stage and lymph node metastasis in CRC patients. (e) MALAT1 expression was upregulated in CRC cells compared to normal colon epithelial cell line (FHC). ANT: adjacent nontumor tissues; CRC: colorectal cancer. ∗p < 0.05. Figure 3 Knockdown of MALAT1 decreases the proliferation and invasion ability of CRC in vitro. (a) MALAT1 expression in SW480 and HCT-8 cells transfected with si-MALAT1 or si-NC. (b, c) MALAT1 inhibition decreased SW480 and HCT-8 cell proliferation and colony formation ability in vitro. (d) MALAT1 knockdown inhibited SW480 and HCT-8 cell invasion ability in vitro. ∗p < 0.05. Figure 4 miR-508-5p expression is downregulated in CRC. (a) The expression of miR-508-5p was decreased in CRC tissues. (b, c) Low miR-508-5p expression was inversely correlated with advanced TNM stage and lymph node metastasis. (d) Low miR-508-5p expression was correlated with worse overall survival in CRC patients. ANT: adjacent nontumor tissues; CRC: colorectal cancer; ∗p < 0.05. Figure 5 MALAT1 functions as the sponge of miR-508-5p in CRC cells. (a) Predicted binding sites in MALAT1 for miR-508-5p. (b) miR-508-5p mimics decreased the luciferase activity of the MALAT1-WT group. (c) MALAT1 inhibition increased miR-508-5p expression in SW480 and HCT-8 cells. (d) RIP assay revealed that the enrichment of MALAT1 was highly elevated by miR-508-5p overexpression in SW480 and HCT-8 cells. (e) MALAT1 expression was inversely associated with miR-508-5p expression in CRC tissues. (f, g) miR-508-5p mimics rescued the effects of MALAT1 overexpression on HCT-8 cell proliferation and invasion. ∗p < 0.05. Figure 6 MALAT1 knockdown suppresses RAB14 expression by interacting with miR-508-5p. (a) Predicted binding sites in 3′UTR-RAB14 for miR-508-5p. (b) miR-508-5p mimics decreased the luciferase activity of the WT-RAB14 group. (c) miR-508-5p mimics increased miR-508-5p levels in SW480 and HCT-8 cells. (d) miR-508-5p overexpression reduced RAB14 protein expression in SW480 and HCT-8 cells. (e, f) miR-508-5p mimics abolished the effects of MALAT1 overexpression on RAB14 expression in SW480 and HCT-8 cells. ∗p < 0.05. Figure 7 RAB14 is highly expressed in CRC. (a, b) GEPAI analysis determined RAB14 expression in CRC tissues. (c, d) RAB14 expression in CRC tissues was determined by qRT-PCR and IHC analysis. (e) High RAB14 levels were correlated with poor disease-free survival in CRC patients. (f) RAB14 knockdown reduced SW480 cell invasion ability. (g) MALAT1 promoted CRC progression by targeting the miR-508-5p/RAB14 axis. COAD: colon adenocarcinoma; READ: rectum adenocarcinoma; ANT: adjacent nontumor tissues; CRC: colorectal cancer; T: tumor tissues; N: normal tissues; ∗p < 0.05. Table 1 Clinicopathological features of CRC patients. Patient characteristics Group Total Gender Male 24 Female 19 Age (years) <60 14 ≥60 29 Tumor size (cm) <5 cm 21 ≥5 cm 22 TNM stage I/II 19 III/IV 24 Lymph node metastasis Negative 23 Positive 20 ==== Refs 1 Bray F. Ferlay J. Soerjomataram I. Siegel R. L. Torre L. A. Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries CA: a Cancer Journal for Clinicians 2018 68 6 394 424 10.3322/caac.21492 2-s2.0-85053395052 30207593 2 Rougier P. Mitry E. Epidemiology, treatment and chemoprevention in colorectal cancer Annals of Oncology 2003 14 supplement 2 ii3 ii5 10.1093/annonc/mdg722 12810450 3 Aran V. Victorino A. P. Thuler L. C. Ferreira C. G. Colorectal cancer: epidemiology, disease mechanisms and interventions to reduce onset and mortality Clinical Colorectal Cancer 2016 15 3 195 203 10.1016/j.clcc.2016.02.008 2-s2.0-84959466627 26964802 4 Marley A. R. Nan H. Epidemiology of colorectal cancer International journal of molecular epidemiology and genetics 2016 7 3 105 114 27766137 5 Mercer T. R. Dinger M. E. Mattick J. S. Long non-coding RNAs: insights into functions Nature Reviews Genetics 2009 10 3 155 159 10.1038/nrg2521 2-s2.0-60349120914 19188922 6 Fatica A. Bozzoni I. Long non-coding RNAs: new players in cell differentiation and development Nature Reviews Genetics 2014 15 1 7 21 10.1038/nrg3606 2-s2.0-84890559595 24296535 7 Gibb E. A. Brown C. J. Lam W. L. The functional role of long non-coding RNA in human carcinomas Molecular Cancer 2011 10 1 10.1186/1476-4598-10-38 2-s2.0-79953888460 8 Zhu L. Xu P. C. Downregulated LncRNA-ANCR promotes osteoblast differentiation by targeting EZH2 and regulating Runx2 expression Biochemical and Biophysical Research Communications 2013 432 4 612 617 10.1016/j.bbrc.2013.02.036 2-s2.0-84875496875 23438432 9 Xiong H. Ni Z. He J. LncRNA HULC triggers autophagy via stabilizing Sirt1 and attenuates the chemosensitivity of HCC cells Oncogene 2017 36 25 3528 3540 10.1038/onc.2016.521 2-s2.0-85011681742 28166203 10 Sun M. Nie F. Wang Y. LncRNA HOXA11-AS promotes proliferation and invasion of gastric cancer by scaffolding the chromatin modification factors PRC2, LSD1, and DNMT1 Cancer Research 2016 76 21 6299 6310 10.1158/0008-5472.CAN-16-0356 2-s2.0-84995680603 27651312 11 Tseng J. J. Hsieh Y. T. Hsu S. L. Chou M. M. Metastasis associated lung adenocarcinoma transcript 1 is up-regulated in placenta previa increta/percreta and strongly associated with trophoblast-like cell invasion in vitro Molecular Human Reproduction 2009 15 11 725 731 10.1093/molehr/gap071 2-s2.0-74049089365 19690017 12 Zhang H. Yang F. Chen S. J. Che J. Zheng J. H. Upregulation of long non-coding RNA MALAT1 correlates with tumor progression and poor prognosis in clear cell renal cell carcinoma Tumor Biology 2015 36 4 2947 2955 10.1007/s13277-014-2925-6 2-s2.0-84931416215 25480417 13 Wu X. S. Wang X. A. Wu W. G. MALAT1 promotes the proliferation and metastasis of gallbladder cancer cells by activating the ERK/MAPK pathway Cancer Biology & Therapy 2014 15 6 806 814 10.4161/cbt.28584 2-s2.0-84901715681 24658096 14 Xie H. Liao X. Chen Z. LncRNA MALAT1 inhibits apoptosis and promotes invasion by antagonizing miR-125b in bladder cancer cells Journal of Cancer 2017 8 18 3803 3811 10.7150/jca.21228 2-s2.0-85032567264 29151968 15 Lu W. Zhang H. Niu Y. Long non-coding RNA linc00673 regulated non-small cell lung cancer proliferation, migration, invasion and epithelial mesenchymal transition by sponging miR-150-5p Molecular Cancer 2017 16 1 10.1186/s12943-017-0685-9 2-s2.0-85022066815 28697764 16 Liz J. Esteller M. lncRNAs and microRNAs with a role in cancer development Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms 2016 1859 1 169 176 10.1016/j.bbagrm.2015.06.015 2-s2.0-84953351370 26149773 17 Tang Z. Li C. Kang B. Gao G. Li C. Zhang Z. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses Nucleic Acids Research 2017 45 W1 W98 W102 10.1093/nar/gkx247 2-s2.0-85023171204 28407145 18 Huarte M. The emerging role of lncRNAs in cancer Nature Medicine 2015 21 11 1253 1261 10.1038/nm.3981 2-s2.0-84946196880 26540387 19 Liu Y. Zhang M. Liang L. Li J. Chen Y. X. Over-expression of lncRNA DANCR is associated with advanced tumor progression and poor prognosis in patients with colorectal cancer International Journal of Clinical and Experimental Pathology 2015 8 9 11480 11484 26617879 20 Wang Y. Kuang H. Xue J. Liao L. Yin F. Zhou X. LncRNA AB073614 regulates proliferation and metastasis of colorectal cancer cells via the PI3K/AKT signaling pathway Biomedicine & Pharmacotherapy 2017 93 1230 1237 10.1016/j.biopha.2017.07.024 2-s2.0-85024904553 28738539 21 Han P. Li J. Zhang B. The lncRNA CRNDE promotes colorectal cancer cell proliferation and chemoresistance via miR-181a-5p-mediated regulation of Wnt/β -catenin signaling Molecular Cancer 2017 16 1 10.1186/s12943-017-0583-1 2-s2.0-85009429506 28086904 22 Yang M. H. Hu Z. Y. Xu C. MALAT1 promotes colorectal cancer cell proliferation/migration/invasion via PRKA kinase anchor protein 9 Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease 2015 1852 1 166 174 10.1016/j.bbadis.2014.11.013 2-s2.0-84913553855 25446987 23 Ji Q. Liu X. Fu X. Resveratrol inhibits invasion and metastasis of colorectal cancer cells via MALAT1 mediated Wnt/β -catenin signal pathway PLoS One 2013 8 11, article e78700 10.1371/journal.pone.0078700 2-s2.0-84892929980 24244343 24 Zhuang M. Zhao S. Jiang Z. MALAT1 sponges miR-106b-5p to promote the invasion and metastasis of colorectal cancer via SLAIN2 enhanced microtubules mobility EBioMedicine 2019 41 286 298 10.1016/j.ebiom.2018.12.049 2-s2.0-85061747147 30797712 25 Wu S. G. Huang Y. J. Bao B. miR-508-5p acts as an anti-oncogene by targeting MESDC1 in hepatocellular carcinoma Neoplasma 2017 64 1 40 47 10.4149/neo_2017_105 2-s2.0-85020475211 27881003 26 Bao G. Wang N. Li R. Xu G. Liu P. He B. miR-508-5p inhibits the progression of glioma by targeting glycoprotein non-metastatic melanoma B Neurochemical Research 2016 41 7 1684 1690 10.1007/s11064-016-1884-2 2-s2.0-84961837650 27003587 27 Shang Y. Zhang Z. Liu Z. miR-508-5p regulates multidrug resistance of gastric cancer by targeting ABCB1 and ZNRD1 Oncogene 2014 33 25 3267 3276 10.1038/onc.2013.297 2-s2.0-84908022850 23893241 28 Kyei G. B. Vergne I. Chua J. Rab14 is critical for maintenance of Mycobacterium tuberculosis phagosome maturation arrest The EMBO Journal 2006 25 22 5250 5259 10.1038/sj.emboj.7601407 2-s2.0-33751115464 17082769 29 Guo B. Wang W. Zhao Z. Rab14 act as oncogene and induce proliferation of gastric cancer cells via AKT signaling pathway PLoS One 2017 12 1, article e0170620 10.1371/journal.pone.0170620 2-s2.0-85010424197 28107526 30 Wang R. Wang Z. X. Yang J. S. Pan X. de W. Chen L. B. MicroRNA-451 functions as a tumor suppressor in human non-small cell lung cancer by targeting ras-related protein 14 (RAB14) Oncogene 2011 30 23 2644 2658 10.1038/onc.2010.642 2-s2.0-79958288052 21358675 31 Wang B. Yin M. Cheng C. Decreased expression of miR-490-3p in colorectal cancer predicts poor prognosis and promotes cell proliferation and invasion by targeting RAB14 International Journal of Oncology 2018 53 3 1247 1256 10.3892/ijo.2018.4444 2-s2.0-85052017871 29916545