Overexpression of the long noncoding RNA CCAT1 promotes metastasis via epithelial‑to‑mesenchymal transition in lung adenocarcinoma

  • Authors:
    • Heping Lin
    • Wei Cheng
    • Hanhan Yan
    • Xiaodiao Zhang
  • View Affiliations

  • Published online on: May 25, 2018     https://doi.org/10.3892/ol.2018.8813
  • Pages: 1809-1814
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

The long noncoding RNA (lncRNA) colon cancer‑associated transcript 1 (CCAT1) has been identified as an oncogene in multiple types of human malignancy, and the aberrant expression of CCAT1 has been associated with the tumorigenesis and progression of cancer. However, the underlying mechanism of how CCAT1 affects malignant behaviors in lung adenocarcinoma cells remains unknown. In the current study, the expression of CCAT1 was identified to be increased in lung adenocarcinoma tissues (n=96) by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR), and its expression level was associated with epidermal growth factor receptor (EGFR) expression (P=0.011), lymphatic metastasis (P=0.003) and tumor node metastasis (TNM) stage (P=0.003). In vitro, by using Transwell assays, the overexpression of CCAT1 was demonstrated to promote the migration and invasion of H358 lung adenocarcinoma cells; while downregulation of CCAT1 expression inhibited H1650 cell migration and invasion. Furthermore, western blot analysis indicated that aberrant CCAT1 expression may induce epithelial‑to‑mesenchymal transition (EMT) by regulating the expression levels of EMT markers (E‑cadherin, N‑cadherin and vimentin). In conclusion, these results indicate that CCAT1 is able to promote the metastasis of lung adenocarcinoma cells by inducing EMT.

Introduction

Lung cancer is one of the most common causes of cancer-associated mortality and has amongst the highest morbidity rates of all types of malignancy in China (1). Non-small cell lung cancer (NSCLC) accounts for 80–85% of all lung cancer cases, with lung adenocarcinoma being the most common type (2). Irrespective of the progress made in diagnosis and therapy, the prognosis of patients with lung adenocarcinoma remains poor (2). A primary feature of lung adenocarcinoma is the migration and invasion of neoplasms, which are responsible for the high mortality rate (3). Therefore, understanding the mechanisms underlying metastasis in lung adenocarcinoma may reveal novel therapeutic targets.

Colon cancer-associated transcript 1 (CCAT1), also known as CARLo-5 (onco-lncRNA-40), is a long noncoding RNA (lncRNA) whose gene is located at chromosome 8q24.21, and was originally identified as an oncogene in colon cancer (4). Aberrant expression of CCAT1 in cancer cells significantly affects cell-cycle regulation and tumor development, and CCAT1 expression has been shown to predict the prognosis of patients with various tumor types (58). However, little is known about the expression levels of CCAT1 in lung adenocarcinoma or whether this lncRNA is involved in the progression of lung adenocarcinoma.

In the present study, the expression level and the function of CCAT1 in lung adenocarcinoma were investigated. The results demonstrated that CCAT1 was upregulated in lung adenocarcinoma tissues, and promoted the migration and invasion of lung adenocarcinoma cells by inducing epithelial-to-mesenchymal transition (EMT).

Materials and methods

Patients and specimens

Lung adenocarcinoma tissues (n=96, aged 39–80 years; mean, 60.0 years) and pair-matched adjacent normal tissues were obtained from patients diagnosed with lung adenocarcinoma of tumor-node-metastasis (TNM) stage I–III. All patients were diagnosed between August 2010 and August 2011 at The Third Affiliated Hospital of Wenzhou Medical University (Wenzhou, China). The exclusion criteria included previous diagnosis with respiratory system diseases, metastasis and patients receiving radiotherapy or chemotherapy prior to their enrollment in the present study. In order to examine tumor cell concentration, frozen sections from all resected fresh tissues underwent histological analyses, and only samples with a tumor cell concentration >60% were included in the present study. Samples were immediately frozen in liquid nitrogen and stored at −80°C until use. Informed consent was obtained from each patient, and the study was approved by the Ethics Committee of The Third Affiliated Hospital of Wenzhou Medical University. Patient data are summarized in Table I.

Table I.

The associations between CCAT1 expression and clinicopathological parameters.

Table I.

The associations between CCAT1 expression and clinicopathological parameters.

CCAT1 expression, n

CharacteristicsNo. of patientsLowHighP-value
Age (years) 0.231
  ≤60804040
  >60322012
Sex 0.860
  Male573126
  Female552926
EGFR 0.011
  Negative744628
  Positive381424
pT 0.539
  1472819
  2582929
  3633
  4101
pN 0.003
  0634320
  11147
  2351124
  3321
pTNM stage 0.003
  I533617
  II21129
  III381226

[i] Data were analyzed using the χ2 test. CCAT1, colon cancer-associated transcript 1; EGFR, epidermal growth factor receptor; pT, pathological tumor stage; pN, pathological node stage; pTNM stage, pathological Tumor-Node-Metastasis stage.

Cell culture

Human lung cancer cell lines (H358, H23, H1975, H1650, H1299 and A549) and a normal human bronchial epithelial cell line (16HBE) were obtained from the Cell Bank of Type Culture Collection of the Chinese Academy of Sciences (Shanghai, China). Cells were cultured in Invitrogen RPMI-1640 medium with 10% fetal bovine serum (FBS) and 100 U/ml penicillin (all from Gibco; Thermo Fisher Scientific, Inc., Waltham, MA, USA) at 37°C in humidified air with 5% CO2.

Reagents and transfection

cDNA of human CCAT1 gene was synthesized by PrimeScript RT Master Mix kit (Takara Bio, Inc., Otsu, Japan). The cDNA encoding CCAT1 was amplified by polymerase chain reaction (PCR) and subcloned into the pcDNA3.1 vector (Invitrogen, Thermo Fisher Scientific, Inc.). The empty vector was used as a negative control. All primary antibodies E-cadherin (cat no. SAB4503751), N-cadherin (cat no. SAB5500023), vimentin (cat no. SAB4503083) and goat anti-rabbit IgG secondary antibody (A0545) were purchased from Sigma-Aldrich (Merck KGaA, Darmstadt, Germany). The anti-human siRNA specifically targeting CCAT1 (synthesized by Thermo Fisher Scientific, Inc.) was used: 5′-CGGCAGGCATTAGAGATGAACAGCA-3′; and the scramble siRNA was used: 5′-CCUACGCCACCAAUUUCGU-3′. Cells were transfected using a Lipofectamine 3000 kit (Thermo Fisher Scientific, Inc.) according to the manufacturer's protocol. Cells were transfected for 48 h prior to their use in CCAT1 expression analyses.

Reverse transcription-quantitative PCR (RT-qPCR)

Total RNA from the collected tissues was extracted using TRIzol reagent (Thermo Fisher Scientific, Inc.) according to the manufacturer's protocol, and cDNAs from all samples were synthesized by PrimeScript RT Master Mix kit (Kusatsu, Japan) and incubated for 30 min at 37°C, 5 sec at 85°C, and then maintained at 4°C. The expression of CCAT1 was quantified using a Quantifast SYBR-Green RT-qPCR kit (Qiagen, GmbH, Hilden, Germany). The primer sequences used were as follows: CCAT1 forward, 5′-CATTGGGAAAGGTGCCGAGA-3′; CCAT1 reverse, 5′-ACGCTTAGCCATACAGAGCC-3′; β-actin forward, 5′-AGCGAGCATCCCCCAAAGTT-3′; and β-actin reverse, 5′-GGGCACGAAGGCTCATCATT-3′. PCR was then performed at 94°C for 2 min, followed by 40 cycles of 95°C for 10 sec and 60°C for 30 sec. Each experiment was repeated independently three times. Gene expression levels were analyzed using the 2−ΔΔCq method (9).

Transwell assay

For the migration and invasion assays, 48 h after transfection, 3×104 cells in serum-free RPMI-1640 medium were placed into the upper chamber of each Transwell insert (8.0 µm; Millipore, Merck KGaA, Darmstadt, Germany). The chambers were pre-coated with Matrigel (Sigma-Aldrich; Merck KGaA, Darmstadt, Germany) for the invasion assays. The chambers were then incubated for 24 h at 37°C in a 5% CO2 incubator, with RPMI-1640 containing 10% FBS in the bottom chambers. Following incubation, cells on the upper surface were scraped off with a cotton swab and washed away with PBS (Invitrogen; Thermo Fisher Scientific, Inc.) and the invaded cells on the lower surface were fixed in 100% precooled methanol for 10 min and stained with 0.5% crystal violet for 2 h. Finally, the number of invaded cells relative to the control group was calculated by counting three fields per membrane under an inverted biological microscope (magnification, ×200). Experiments were independently repeated in triplicate.

Western blot analysis

Cells were lysed in RIPA buffer (Sigma-Aldrich; Merck KGaA) supplemented with a protease inhibitor (Roche, Basel, Switzerland) and a phosphatase inhibitor (Roche). Protein concentration was measured using a BCA protein Assay kit (Thermo Fisher Scientific, Inc.). Total protein lysates (25 µg) were fractionated by 10% sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and were electrophoretically transferred to polyvinylidene difluoride membranes (Roche). Enhanced chemiluminescence (Tiangen Biotech Co., Ltd., Beijing, China) was used to visualize the antibody binding. Equal protein loading was controlled by using a mouse anti-β-actin monoclonal antibody. The membranes were blocked with 10% non-fat milk in Tris-buffered saline Tween (TBST) for 2 h at room temperature, washed and then probed with the primary antibodies (dilution 1:100) overnight at 4°C, followed by incubation with the goat anti-rabbit IgG secondary antibody conjugated to horseradish peroxidase (dilution 1:2,000, TBST dilution) for 2 h at room temperature. The membranes were then washed three times for 15 min with PBST. Proteins were detected using a Molecular Imager ChemiDoc XRS System (Bio-Rad Laboratories, Inc., Hercules, CA, USA). The integrated densities of the bands were quantified by ImageJ version software (v1.7.0, National Institutes of Health, Bethesda, MD, USA).

Statistical analysis

Statistical analysis was performed and presented using GraphPad Prism version 6.0 (GraphPad Software Inc., La Jolla, CA, USA). The data obtained from in vitro assays were analyzed by paired Student's t-test, χ2 test, Wilcoxon rank-sum (Mann-Whitney) test or one-way ANOVA followed by Tukey's multiple comparison tests, as appropriate. All tests performed were two-sided. P<0.05 was considered to indicate a statistically significant difference.

lncRNA CCAT1 is upregulated in human lung adenocarcinoma tissues and cell lines

The expression levels of CCAT1 were analyzed in cancer tissues (n=96) and adjacent normal tissues from patients with lung adenocarcinoma by RT-qPCR. The results indicated that CCAT1 expression, relative to β-actin, was significantly higher in lung adenocarcinoma tissues than adjacent normal tissues (P<0.001; Fig. 1A). To further investigate the associations between clinicopathological features and CCAT1 expression levels, the mean CCAT1 expression level among all lung adenocarcinoma tissues (mean, 13.33) was used as the cutoff value. All 96 patients were divided into a low-CCAT1 expression group (n=60) and a high-CCAT1 expression group (n=56). CCAT1 expression was significantly associated with EGFR expression (P=0.011), lymphatic metastasis (P=0.003) and TNM stage (P=0.003), whereas no significant association with age or sex were observed (Table I). The expression of CCAT1 was then detected in lung adenocarcinoma cell lines (H358, H23, H1975, H1650, H1299 and A549) and a normal human bronchial epithelial cell line (16HBE). The RT-qPCR assay indicated that CCAT1 was higher in all lung adenocarcinoma cell lines than in the normal lung cell line (P<0.01; Fig. 1B). Based on CCAT1 expression patterns, the H358 and H1650 cell lines were selected to detect the effect of lncRNA CCAT1 in in vitro experiments.

CCAT1 regulates the migration and invasion of lung adenocarcinoma cell lines in vitro

To explore the biological functions of CCAT1 in the cell migration and invasion of lung adenocarcinoma, CCAT1 expression was upregulated in H358 cells by transfection with a pcDNA3.1-CCAT1 plasmid, and downregulated in H1650 cells by interfering with siRNA. The transfection efficiency was determined by RT-qPCR (Fig. 2A). A Transwell assay indicated that upregulation of CCAT1 promoted the migration of H358 cells, while suppression of CCAT1 inhibited the migration of H1650 cells, (P<0.01; Fig. 2B). Furthermore, upregulated CCAT1 increased H358 cell invasion, while knockdown of CCAT1 suppressed H1650 cell invasion (P<0.01; Fig. 2C). The results suggested that aberrant expression of CCAT1 acts to regulate lung adenocarcinoma cell metastasis.

lncRNA CCAT1 influences the expression of EMT-associated markers in lung adenocarcinoma

To explore whether aberrant CCAT1 expression levels were involved in the process of EMT, the mesenchymal markers N-cadherin and vimentin, and the epithelial marker E-cadherin were investigated by western blotting. Overexpression of CCAT1 in H358 cells resulted in upregulation of N-cadherin and vimentin protein expression and downregulation of E-cadherin protein; while knockdown of CCAT1 expression in H1650 cells resulted in downregulation of N-cadherin and vimentin protein expression and upregulation of E-cadherin protein (P<0.01; Fig. 3). This indicates that CCAT1 may contribute to the regulation of EMT-associated marker expression in lung adenocarcinoma cell lines.

Discussion

In the present study, the expression of the lncRNA CCAT1 and its biological effect on tumor cell metastasis in lung adenocarcinoma were detected and investigated, and it was confirmed that CCAT1 is upregulated in lung adenocarcinoma. Clinically, high expression levels of CCAT1 were associated with EGFR expression, lymphatic metastasis and tumor stage. The clinical results indicated that CCAT1 may be involved in the development of lung adenocarcinoma. Furthermore, upregulation of CCAT1 promoted the migration and invasion of lung adenocarcinoma cell lines, and downregulation of CCAT1 inhibited cell migration and invasion in vitro. Additionally, the results demonstrated that CCAT1 may induce EMT to promote cell metastasis in lung adenocarcinoma.

lncRNAs have been reported to serve important regulatory roles in the biology of human malignancy (10). Specifically for lung adenocarcinoma, it has already been reported that lncRNAs contribute to the malignant phenotype of tumor cells (1116). The lncRNA CCAT1 (NR_108049.1) was initially identified as a strongly upregulated noncoding transcript (2,795 bases in humans) in colon cancer, and high CCAT1 expression is associated with metastasis in colon cancer (17). Recently, Chen et al (18) identified that CCAT1 is responsible for docetaxel resistance in lung adenocarcinoma cells. The present study demonstrated that CCAT1 was significantly increased in the patient-derived lung adenocarcinoma tissues compared with the corresponding normal tissues, with the expression of CCAT1 in lung cancer cell lines further confirming the results. Additionally, due to the positive association between CCAT1 and high tumor burden (CCAT1 expression was significantly associated with lymphatic metastasis and TNM stage), cell migration and invasion assays were performed. The results suggested that upregulation of CCAT1 induced cell migration and invasion, while downregulation of CCAT1 inhibited cell metastasis, which meant that CCAT1 could promote the malignant phenotype of lung adenocarcinoma, with the results being consistent with those of Luo et al (19). Mechanistically, CCAT1 functions as an oncogene in lung adenocarcinoma through the upregulation of EMT-associated proteins.

EGFR status is a critical factor for the selection of therapeutic strategy in patients with lung adenocarcinoma. In the present study, the results indicated that CCAT1 expression was associated with EGFR status; as EGFR-mutated NSCLC patients can benefit from EGFR-tyrosine kinase inhibitor (TKI) therapies, genes associated with EGFR status may also act as pivotal therapeutic targets. The mechanisms underlying this relationship remain unclear; therefore future studies should focus on the role of CCAT1 in EGFR mutation, and whether it is involved in the development of resistance to EGFR-TKIs in lung cancer. Previous studies have implicated the activation of EMT in resistance to EGFR-TKIs; activation of EMT can suppress E-cadherin and directly reduce sensitivity to EGFR-TKIs (20,21). As a secondary mutation, T790M is the most common mechanism for acquisition of EGFR-TKI resistance (in 50–60% of cases) (22). Since CCAT1 is an EMT-promoting lncRNA, CCAT1 may also act as a promotion molecule overcoming EGFR-TKI resistance.

Previous studies have demonstrated that CCAT1 can interact with MYC enhancer in colorectal and prostate cancer and, in turn, regulate long-range chromatin interactions at the MYC locus (4), acting as an oncogene sponge in human gallbladder cancer and hepatocellular carcinoma, partly by repressing miRNAs (8,23). CCAT1 can also promote the acquisition of chemoresistance and EMT phenotypes in docetaxel-resistant lung adenocarcinoma cells by competitively binding with let-7c (18). However, as the molecular mechanism of a particular lncRNA may differ in different tumor microenvironments, histological subtypes and tumor stages, CCAT1 may regulate lung adenocarcinoma cell metastasis and EMT phenotypes through different potential targets, and the specific target genes controlled by CCAT1 in lung adenocarcinoma require further studies for clarification.

Taken together, the findings of the present study indicate that aberrant expression of CCAT1 is associated with EGFR status, tumor metastasis and tumor stage in lung adenocarcinoma. In addition, overexpression of CCAT1 promotes metastasis via the induction of EMT in vitro. Further research may identify a way in which the pathway linking CCAT1 and EMT may be exploited as a therapeutic approach for the treatment of lung adenocarcinoma.

Acknowledgements

Not applicable.

Funding

No funding received.

Availability of data and materials

The datasets generated in the present study are available on reasonable request from the corresponding author.

Authors' contributions

HL participated in the design of the study and performed the statistical analysis. XZ, WC and HY conceived the study, participated in its design and execution, and helped to draft the manuscript. All authors read and approved the final manuscript.

Ethics approval and consent to participate

Informed consent was obtained from each patient, and the study was approved by the Ethics Committee of The Third Affiliated Hospital of Wenzhou Medical University (Wenzhou, China).

Consent for publication

Consent for publication was obtained from the study participants.

Competing interests

The authors declare that they have no competing interests.

References

1 

Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in China, 2015. CA Cancer J Clin. 66:115–132. 2016. View Article : Google Scholar : PubMed/NCBI

2 

Rosell R and Karachaliou N: Lung cancer: Maintenance therapy and precision medicine in NSCLC. Nat Rev Clin Oncol. 10:549–550. 2013. View Article : Google Scholar : PubMed/NCBI

3 

Wood SL, Pernemalm M, Crosbie PA and Whetton AD: The role of the tumor-microenvironment in lung cancer-metastasis and its relationship to potential therapeutic targets. Cancer Treat Rev. 40:558–566. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Xiang JF, Yin QF, Chen T, Zhang Y, Zhang XO, Wu Z, Zhang S, Wang HB, Ge J, Lu X, et al: Human colorectal cancer-specific CCAT1-L lncRNA regulates long-range chromatin interactions at the MYC locus. Cell Res. 24:513–531. 2014. View Article : Google Scholar : PubMed/NCBI

5 

Zhu HQ, Zhou X, Chang H, Li HG, Liu FF, Ma CQ and Lu J: Aberrant expression of CCAT1 regulated by c-Myc predicts the prognosis of hepatocellular carcinoma. Asian Pac J Cancer Prev. 16:5181–5185. 2015. View Article : Google Scholar : PubMed/NCBI

6 

Wang F, Xie C, Zhao W, Deng Z, Yang H and Fang Q: Long non-coding RNA CARLo-5 expression is associated with disease progression and predicts outcome in hepatocellular carcinoma patients. Clin Exp Med. 17:33–43. 2017. View Article : Google Scholar : PubMed/NCBI

7 

Yang F, Xue X, Bi J, Zheng L, Zhi K, Gu Y and Fang G: Long noncoding RNA CCAT1, which could be activated by c-Myc, promotes the progression of gastric carcinoma. J Cancer Res Clin Oncol. 139:437–445. 2013. View Article : Google Scholar : PubMed/NCBI

8 

Kim T, Cui R, Jeon YJ, Lee JH, Lee JH, Sim H, Park JK, Fadda P, Tili E, Nakanishi H, et al: Long-range interaction and correlation between MYC enhancer and oncogenic long noncoding RNA CARLo-5. Proc Natl Acad Sci USA. 111:4173–4178. 2014. View Article : Google Scholar : PubMed/NCBI

9 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

10 

Beermann J, Piccoli MT, Viereck J and Thum T: Non-coding RNAs in development and disease: Background, mechanisms, and therapeutic approaches. Physiol Rev. 96:1297–1325. 2016. View Article : Google Scholar : PubMed/NCBI

11 

Yang YR, Zang SZ, Zhong CL, Li YX, Zhao SS and Feng XJ: Increased expression of the lncRNA PVT1 promotes tumorigenesis in non-small cell lung cancer. Int J Clin Exp Pathol. 7:6929–6935. 2014.PubMed/NCBI

12 

Nie FQ, Sun M, Yang JS, Xie M, Xu TP, Xia R, Liu YW, Liu XH, Zhang EB, Lu KH and Shu YQ: Long noncoding RNA ANRIL promotes non-small cell lung cancer cell proliferation and inhibits apoptosis by silencing KLF2 and P21 expression. Mol Cancer Ther. 14:268–277. 2015. View Article : Google Scholar : PubMed/NCBI

13 

Nie W, Ge HJ, Yang XQ, Sun X, Huang H, Tao X, Chen WS and Li B: LncRNA-UCA1 exerts oncogenic functions in non-small cell lung cancer by targeting miR-193a-3p. Cancer Lett. 371:99–106. 2016. View Article : Google Scholar : PubMed/NCBI

14 

Shen L, Chen L, Wang Y, Jiang X, Xia H and Zhuang Z: Long noncoding RNA MALAT1 promotes brain metastasis by inducing epithelial-mesenchymal transition in lung cancer. J Neurooncol. 121:101–108. 2015. View Article : Google Scholar : PubMed/NCBI

15 

Wang G, Chen H and Liu J: The long noncoding RNA LINC01207 promotes proliferation of lung adenocarcinoma. Am J Cancer Res. 5:3162–3173. 2015.PubMed/NCBI

16 

Wu Y, Liu H, Shi X, Yao Y, Yang W and Song Y: The long non-coding RNA HNF1A-AS1 regulates proliferation and metastasis in lung adenocarcinoma. Oncotarget. 6:9160–9172. 2015.PubMed/NCBI

17 

Alaiyan B, Ilyayev N, Stojadinovic A, Izadjoo M, Roistacher M, Pavlov V, Tzivin V, Halle D, Pan H, Trink B, et al: Differential expression of colon cancer associated transcript1 (CCAT1) along the colonic adenoma-carcinoma sequence. BMC Cancer. 13:1962013. View Article : Google Scholar : PubMed/NCBI

18 

Chen J, Zhang K, Song H, Wang R, Chu X and Chen L: Long noncoding RNA CCAT1 acts as an oncogene and promotes chemoresistance in docetaxel-resistant lung adenocarcinoma cells. Oncotarget. 7:62474–62489. 2016.PubMed/NCBI

19 

Luo J, Tang L, Zhang J, Ni J, Zhang HP, Zhang L, Xu JF and Zheng D: Long non-coding RNA CARLo-5 is a negative prognostic factor and exhibits tumor pro-oncogenic activity in non-small cell lung cancer. Tumour Biol. 35:11541–11549. 2014. View Article : Google Scholar : PubMed/NCBI

20 

Hampton KK and Craven RJ: Pathways driving the endocytosis of mutant and wild-type EGFR in cancer. Oncoscience. 1:504–512. 2014. View Article : Google Scholar : PubMed/NCBI

21 

Rolfo C, Giovannetti E, Hong DS, Bivona T, Raez LE, Bronte G, Buffoni L, Reguart N, Santos ES, Germonpre P, et al: Novel therapeutic strategies for patients with NSCLC that do not respond to treatment with EGFR inhibitors. Cancer Treat Rev. 40:990–1004. 2014. View Article : Google Scholar : PubMed/NCBI

22 

Sequist LV, Waltman BA, Dias-Santagata D, Digumarthy S, Turke AB, Fidias P, Bergethon K, Shaw AT, Gettinger S, Cosper AK, et al: Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci Transl Med. 3:75ra262011. View Article : Google Scholar : PubMed/NCBI

23 

Ma MZ, Chu BF, Zhang Y, Weng MZ, Qin YY, Gong W and Quan ZW: Long non-coding RNA CCAT1 promotes gallbladder cancer development via negative modulation of miRNA-218-5p. Cell Death Dis. 6:e15832015. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

August-2018
Volume 16 Issue 2

Print ISSN: 1792-1074
Online ISSN:1792-1082

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Lin H, Cheng W, Yan H and Zhang X: Overexpression of the long noncoding RNA CCAT1 promotes metastasis via epithelial‑to‑mesenchymal transition in lung adenocarcinoma. Oncol Lett 16: 1809-1814, 2018
APA
Lin, H., Cheng, W., Yan, H., & Zhang, X. (2018). Overexpression of the long noncoding RNA CCAT1 promotes metastasis via epithelial‑to‑mesenchymal transition in lung adenocarcinoma. Oncology Letters, 16, 1809-1814. https://doi.org/10.3892/ol.2018.8813
MLA
Lin, H., Cheng, W., Yan, H., Zhang, X."Overexpression of the long noncoding RNA CCAT1 promotes metastasis via epithelial‑to‑mesenchymal transition in lung adenocarcinoma". Oncology Letters 16.2 (2018): 1809-1814.
Chicago
Lin, H., Cheng, W., Yan, H., Zhang, X."Overexpression of the long noncoding RNA CCAT1 promotes metastasis via epithelial‑to‑mesenchymal transition in lung adenocarcinoma". Oncology Letters 16, no. 2 (2018): 1809-1814. https://doi.org/10.3892/ol.2018.8813