#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Long Non-Cod­ing RNA Signature in Cervical Cancer


Dlouhé nekódující molekuly RNA u cervikálních nádorů

Východiska:

Rakovina děložního čípku jako běžný urogenitální nádor způsobuje u žen značné zdravotní problémy. Byla vynaložena snaha o identifikaci patogeneze za účelem nalezení cílených terapií. Bylo prokázáno, že dlouhé nekódující ribonukleové kyseliny (lncRNA) regulují několik signálních drah a genů souvisejících s nádory, což přispívá k patogenezi lidských malignit vč. rakoviny děložního čípku. V rámci prezentovaného článku jsme do prosince 2017 vyhledávali klíčová slova „cervical cancer“ (rakovina děložního čípku) nebo „cervical neoplasm“ (cervikální novotvar) a „long non-cod­ing RNA“ (dlouhá nekódující RNA) nebo „lncRNA“, publikovaná v databázi PubMed, Google scholar, Web of Science a Scopus.

Cíl:

Zjistit, jakou roli hrají lncRNA v rakovině děložního čípku.

Závěry:

LncRNA ovlivňují patogenezi rakoviny děložního čípku prostřednictvím četných mechanismů, jako je vytváření tzv. scaffolds pro sestavení proteinových komplexů, sloužící jako tzv. directors pro získávání proteinů, fungujících jako transkripční zesilovače pomocí remodelování chromatinu, sloužící jako tzv. návnady k uvolnění proteinů z chromatinu nebo zvrácení účinků jiné regulační nekódující RNA jako jsou mikroRNA. Analýza signálních drah ukázala, že v procesu patogeneze rakoviny děložního čípku několik lncRNA reguluje dráhy PI3K/Akt/mTOR, Wnt-β catenin a Notch signální dráhy. Navíc exprese několika lncRNA byla spojena s infekcí virem lidského papilomu. Identifikace lncRNA, které mění signální dráhy související s nádory, a následná expresní analýza těchto lncRNA ve vzorcích pa­cientů by mohly pomoci získat efektivní cílené terapie.

Klíčová slova:

lncRNA – nádor děložního čípku – onkogen – tumor supresorový gen

Autoři deklarují, že v souvislosti s předmětem studie nemají žádné komerční zájmy.

Redakční rada potvrzuje, že rukopis práce splnil ICMJE kritéria pro publikace zasílané do biomedicínských časopisů.


Authors: M. Taheri 1;  S. Ghafouri-Fard 2
Authors place of work: Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran 1;  Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran 2
Published in the journal: Klin Onkol 2018; 31(6): 403-408
Category: Přehled
doi: https://doi.org/10.14735/amko2018403

Summary

Background: Cervical cancer as a common urogenital cancer among women has caused significant health problems. Efforts have been made to identify its pathogenic process in order to find targeted ther­apies. Long non-cod­ing ribonucleic acids (lncRNAs) have been shown to regulate several cancer-related pathways and genes that contribute to pathogenesis of human malignancies, includ­ing cervical cancer. In the present review, we searched PubMed, Google scholar, Web of Science and Scopus databases for key words “cervical cancer” or “cervical neoplasm” and “long non-cod­ing RNA” or “lncRNA” (up to December 2017).

Aim: To elaborate the role of lncRNAs in cervical cancer.

Conclusions: LncRNAs affect cervical cancer pathogenesis through numerous mechanisms, such as mak­ing scaffolds for assembly of protein complexes, serv­ing as directors to recruit proteins, function­ing as transcriptional enhancers through chromatin remodeling, serv­ing as decoys to free up proteins from chromatin, or revers­ing the effects of other regulatory non-cod­ing RNAs, such as microRNAs. Pathway-based analysis showed that several lncRNAs modulate PI3K/Akt/mTOR, Wnt-β catenin and Notch pathways in the process of cervical cancer pathogenesis. In addition, expression of a handful of lncRNAs has been associated with human papilloma virus infection. Identification of lncRNAs that alter cancer-related signal­ing pathways and subsequent expression analysis of these lncRNAs in patients’ samples would help to design effective targeted ther­apies.

Key words:

lncRNA – cervical cancer – oncogene – tumor suppressor gene

Introduction

In recent years, progress in genome ana­lyses has led to recognition of an evolv­ing class of non-cod­ing ribonucleic acids (ncRNAs) that participate in the modulation of gene expression and epigenetic reprogramming [1]. A signi­ficant number of these ncRNAs are longer than 200 nucleotides and instead of be­ing transcriptional “noise”, they use various routes to control gene expression [1]. These so-called long non-cod­ing RNA (lncRNAs) have tissue specific expression pattern [2] but are less conserved than protein cod­ing RNAs [3]. They are involved in almost every aspect of physiological processes, such as preservation of DNA integrity [4], telomere bio­logy [5], immune cell homeostasis [6], regulation of hormone receptors [7] as well as differentiation and homeostasis of metabolic tissues [8]. The differential expression of lncRNAs in malignant tissues compared with normal tissues of the same origin has been demonstrated in several studies [3,9–14] what implies their role in pathogenesis of different cancers. Such speculation has been further supported by the presence of distinct single nucleotide polymorphisms within lncRNA cod­ing genes which alter the risk of cancer development [15,16].

Cervical cancer as a common uro­genital cancer among women is mostly associated with human papilloma virus (HPV) infection. However, as its incidence is much lower than the prevalence of HPV infection, other factors are thought to have synergic effects with HPV infection to induce cervical cancer [17]. Dysregulation of Wnt/β-catenin signal­ing as well as PI3K/Akt/mTOR signal­ing pathway have also been implicated in the pathogenesis of cervical cancer [18]. Consider­ing the role of lncRNAs in the regulation of these pathways, we searched the literature to identify lncRNAs that modulate cervical cancer risk especially through alteration of these pathways or through modulation of HPV infection process.    

Search strategy 

We searched PubMed, Google scholar, Web of Science and Scopus databases with the key words “cervical cancer” or “cervical neoplasm” AND “long non-cod­ing RNA” or “lncRNA”. Original articles were chosen if they were written in English and had enough number of samples for expression analysis (at least 20 patients’ samples from exclusive clinical studies) and described the mechanism of lncRNA involvement in cervical cancer (for in vitro studies). Other types of papers were excluded from the study. Papers, which focused on analysis of lncRNAs at genomic level, were also excluded.

LncRNA involvement in cervical cancer

A recent study aimed at identification of expression profiles of lncRNAs, circular RNAs, microRNA (miRNA), and messenger RNA (mRNA) in HPV16 mediated ce­rvical squamous cell carci­noma have found 19 lncRNAs that are frequently differentially expressed in cervical cancer samples compared to normal samples. Such differentially expressed lncRNAs have been shown to participate in cervical cancer pathogenesis as revealed by the co-expression network and function prediction [19]. In addition to this high throughput studies, several studies have assessed the significance of lncRNAs in cervical cancer pathogenesis. Based on the importance of HPV infection and dysregulation of signal­ing pathways in the pathogenesis of cervical cancer, we subsequently analyzed lncRNAs based on their involvement in one of these mechanisms.

LncRNAs and HPV infection

HPVs as double-stranded circular DNA vi­ruses encode several proteins, which participate in their DNA repli­cation, gene transcription and cellular trans­formation. E6 and E7 proteins coded by high-risk HPV viruses participate in the pathogenesis of HPV-associated carcinomas [20]. Degradation of p53 and retinoblastoma protein (Rb) as two important tumor suppressor proteins is induced by the HPV onco­genic proteins E6 and E7, respectively. E6 also participates in carcinogenesis through induction of telomerase activation, while E7 alters the expression of synthesis phase genes by directly disturb­ing pRb/E2F complex and en­hances cell survival by induc­ing ex­pres­-sion of interleukin-648 and anti­apo­-ptotic Mcl-126 and trigger­ing the Akt/PKB pathway [20]. The cooperation of HPV oncogenes and lncRNAs in cervical cancer context has been first revealed for metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). This lncRNA has been over-expressed in cervical cancer cell lines compared with normal cervical squamous cell samples. However, its expression has been decreased follow­ing the E6/E7 knockdown in CaSki cells. Further asses­sment of clinical samples has confirmed exclusive expression of MALAT1 in HPV--positive cervical squamous cells, but not in HPV-negative normal cervical squamous cells [21]. The positive association between MALAT1 expression levels and HPV infection has also been documented in cervical epithelial tissues by microarray analysis [22].

HOX transcript antisense RNA (HOTAIR) participates in epigenetic regulation of gene expression through recruitment of chromatin remodel­ing polycomb repressive complex 2 (PRC2). This lncRNA has been recognized as a target of E7 in HPV16 related cervical cancers. HOTAIR expression has been shown to be progressively decreased in a linear manner from HPV negative controls to HPV16 positive non-malignant and cervical cancer samples. Such down-regulation was concomitant with up-regulation of HOTAIR target, HOXD10, and enhancement of cancer related pathways in most cervical cancer cases. Conversely, a minority of them had considerably higher HOTAIR expression, associated with high E7 expression and enhancement of metastatic pathways. The interaction between HOTAIR and E7 has further been supported by observation of a positive correlation between E7 expression and expressions of both HOTAIR and PRC2 complex members (EZH2 and SUZ12) in cervical cancer cases. In addition, both in silico analysis and RNA immunoprecipitation endorsed the functional inactivation of HOTAIR by direct interaction with E7. Consequently, HOTAIR has been identified as a downstream target of HPV16 E7 in the process of cervical cancer pathogenesis [23].

LncRNAs and PI3K/ Akt/ mTOR pathway

Maternally expressed 3 (MEG3) as a tumor suppressor lncRNA has been impli­cated in cervical cancer. Its over-expres­sion in cervical cancer cells resulted in down-regulation of PI3K, Akt, MMP-2, MMP-9 and Bcl-2 expression while up-regulat­ing Bax and P21 expression. Consequently, lncRNA MEG3 inhibits cervical cancer by modification of PI3K/Akt/Bcl-2/Bax/P21 and PI3K/Akt/MMP-2/9 signal­ing pathway [24]. GAS5 as another tumor suppressor has been shown to modulate cellular growth and drug resistance through the PTEN/PI3KAkt/mTOR pathway. The low level of GAS5 leads to PTEN down-regulation by interact­ing with miR-21 because PTEN is one of the genes in the PI3K/Akt/mTOR pathway whose expression is decreased by GAS5. Eventually, the low expression of PTEN triggers the PI3K/Akt pathway, therefore produc­ing a circulation. Moreover, GAS5 and miR-21 modulate cisplatin resistance in cervical cancer cells via the PI3K/Akt pathway [25].

Mitogen activated protein kinases (MAPK) pathway

TCONS_00026907 as a newly identified lncRNA enhances expression of cyclin D1 and Bcl-2 in vivo and in vitro. Its knock-down inhibits growth of cervical tumors and modulates the expression of ELK1, p-ELK1, c-fos, cyclin D1 and Bcl-2 in vivo. Consider­ing the role of ELK1 as a nuclear target for the Ras-Raf-MAPK signal­ing cascade [26], the oncogenic effect of this lncRNA in cervical cancer might be due to its effect on MAPK pathway.

LncRNAs and Wnt/ β-catenin pathway

The Wnt/β-catenin signal­ing pathway is a quintessential survival pathway which modulates several cellular processes includ­ing proliferation, growth, survival and metabolism. XIST silenc­ing in cervical cancer cells decreased the protein level of β-catenin and inhibited the protein expression of two Wnt/β-catenin down­stream genes – cyclin D1 and c-Myc [27]. Besides, CCAT-1 role in enhancement of proliferation and suppression of apo­ptosis of cervical cancer cells is also through induction of the Wnt/β-catenin pathway [28].

LncRNAs and Notch pathway

Evaluation of the essential signal­ing cascades regulated by Notch in HOTAIR--overexpress­ing cells has shown that HOTAIR overexpression in SiHa cells has led to increased NOTCH1, HES1 and p300 expression [29].

LncRNA involvement in epithelial-mesenchymal transition (EMT) of cervical cancer cells

HOTAIR as an oncogenic lncRNA in cervical cancer has been shown to alter the expression of several genes participated in cell migration, invasion and EMT, such as vascular endothelial growth factor, MMP-9, E-cadherin, β-catenin, vimentin, Snail and Twist [30]. EMT-related levels have also been ele­vated in xenografts originated from HOTAIR-overexpress­ing SiHa cells com­pared with the control tumors [29]. In addition, HOTAIR enhances migration and invasion of HeLa cervical cancer cells, at least partially, through the modulation of vimentin expression [31]. HOTAIR role in EMT might also due to its effect on COX-2 stabilization, which leads to induction of matrix metalloproteinases and vascular endothelial growth factor (Schema 1) [32].

Schema 1. Different roles of HOTAIR in cervical cancer tumorigenesis: HOTAIR has a negative regulatory role on PTEN tumor suppressor
gene. HOTAIR role in EMT is due to its effect on COX-2 stabilization which leads to induction of MMPs and VEGF. HOTAIR also enhances
HLA-G associated immune escape by competitively binding to miR-148a.<br>
lncRNA – long non-coding ribonucleic acid, EMT – epithelial-mesenchymal transition, MMP – matrix metallopeptidase, VEGF – vascular
endothelial growth factor, HLA-G – human leukocyte antigen G, PGE2 – prostaglandin E2, COX – cyclooxygenase
Schema 1. Different roles of HOTAIR in cervical cancer tumorigenesis: HOTAIR has a negative regulatory role on PTEN tumor suppressor gene. HOTAIR role in EMT is due to its effect on COX-2 stabilization which leads to induction of MMPs and VEGF. HOTAIR also enhances HLA-G associated immune escape by competitively binding to miR-148a.
lncRNA – long non-coding ribonucleic acid, EMT – epithelial-mesenchymal transition, MMP – matrix metallopeptidase, VEGF – vascular endothelial growth factor, HLA-G – human leukocyte antigen G, PGE2 – prostaglandin E2, COX – cyclooxygenase

MALAT1 exerts its role in cervical cancer cell invasion and metastasis by enhancement of the EMT process through increas­ing the expression of Snail [33]. MALAT1 silenc­ing suppressed the invasion and metastasis of cervical cancer cells, increased expression of the epithelial markers E-cadherin and ZO-1, and simultaneously decreased expression of mesenchymal markers β-catenin and vimentin as well as the Snail transcription factor (Schema 2) [22].

Schema 2. MALAT1 role in cervical cancer: MALAT1 inhibits epithelial markers E-cadherin and ZO-1, and simultaneously enhances expression
of the mesenchymal markers β-catenin and vimentin as well as the Snail transcription factor.<br>
lncRNA – long non-coding ribonucleic acids, EMT – epithelial-mesenchymal transition, E-cad – E-cadherin
Schema 2. MALAT1 role in cervical cancer: MALAT1 inhibits epithelial markers E-cadherin and ZO-1, and simultaneously enhances expression of the mesenchymal markers β-catenin and vimentin as well as the Snail transcription factor.
lncRNA – long non-coding ribonucleic acids, EMT – epithelial-mesenchymal transition, E-cad – E-cadherin

The lncRNA taurine‐upregulated gene 1(TUG1) was also shown to increase migration and invasion of cervical can­cer cells by modulat­ing EMT‐related markers such as fibronectin, vimentin and cytokeratin [34].

HOXA11-AS has also been shown to participate in EMT. HOXA11-AS silenc­ing has led to increase in E-cadherin expression while decreas­ing levels of β-catenin, vimentin and the EMT-mediat­ing transcription factor Snail [35].

In addition, EZH2-bind­ing lncRNA in cervical cancer (lncRNA-EBIC) has a role in migration and invasion of cervical cancer cells through modulation of E-cadherin [36].

LncRNAs role in cervical cancer immune evasion

The human leukocyte antigen-G (HLA-G) as a member of the non-classical ma­jor histocompatibility complex family is recruited by cancer cells to beat attentive immuno-surveillance of the host. HOTAIR has been shown to en­hance HLA-G associated immune escape by competitively bind­ing to miR-148a (Schema 1) [37].

Discussion

Consistent with diverse mechanisms of lncRNAs participation in regulation of gene expression, lncRNAs can affect cervical cancer pathogenesis through various mechanisms. Over­all, the regulatory function of lncRNAs can be exerted through mak­ing scaffolds for assembly of protein complexes, serv­ing as guides to recruit proteins, function­ing as transcriptional enhancers through chromatin remodeling, serv­ing as decoys to free up proteins from chromatin, or revers­ing the effects of other regulatory ncRNAs, such as miRNAs [38]. Besides, the expression of HPV oncogenes as the most important causal factor in cervical cancer has been shown to be linked to expression levels of some lncRNAs. However, functional studies to reveal the exact mechanism of this association has been performed for only two lncRNAs, namely MALAT1 and HOTAIR. Moreover, expression of several lncRNAs has been shown to be dysregulated in tumor tissues as well as plasma samples from cervical cancer patients. Higher expression of certain lncRNAs in the plasma of cervical cancer patients compared to healthy subjects provides an applicable tool for screen­ing and follow-up of patients.

More importantly, methylation pat­tern of the MEG3 lncRNA has been demonstrated to be a dia­gnostic and prognostic marker of cervical cancer with the capability to predict high--risk HPV infection and lymph node metastasis [39]. Consider­ing the early onset of methylation alterations dur­ing carcinogenesis, identification of such marks is valuable in early detection of cancer.

Notable, several lncRNAs have been shown to affect cancer-related path­ways. Alterations in these pathways modulate response to conventional che­motherapeutic approaches as revealed for cisplatin resistance in cervical can­cer [25]. On the other hand, dysregulation of numerous signal­ing pathways, such as Notch and mTOR pathways, has been demonstrated in cervical cancers through transcriptome analysis. Consider­ing the therapeutic potential of these signal­ing pathways in at least some types of cervical cancer, targeted inhibition of Notch and mTOR pathways has been suggested as therapeutic options for cervical cancer patients [40]. Consequently, identification of lncRNAs that alter these signal­ing pathways and subsequent expression analysis of these lncRNAs in patients’ samples would help to better select patients for recruitment in these trials.

The authors declare they have no potential conflicts of interest concerning drugs, pro­ducts, or services used in the study.

The Editorial Board declares that the manu­script met the ICMJE recommendation for biomedical papers.

Submitted/Obdrženo: 25. 4. 2018

Accepted/Přijato: 1. 11. 2018

Soudeh Ghafouri-Fard, MD, PhD

Department of Medical Genetics

Shahid Beheshti University of Medical Sciences

Bldg No. 2 SBUMS

Arabi Ave, Daneshjoo Blvd, Velenjak

Tehran, Iran

e-mail: s.ghafourifard@sbmu.ac.ir     


Zdroje

1. Wan DC, Wang KC. Long noncod­­ing RNA: significance and potential in skin bio­logy. Cold Spr­­ing Harb Perspect Med 2014; 4(5): pii: a015404. doi: 10.1101/cshperspect.a015404.

2. Dianatpour A, Ghafouri-Fard S. Long non cod­­ing RNA expres­sion intersect­­ing cancer and spermatogenesis: a systematic review. Asian Pac J Cancer Prev 2017; 18(10): 2601–2610. doi: 10.22034/APJCP.2017.18.10.2601.

3. Soudyab M, Iranpour M, Ghafouri-Fard S. The role of long non-cod­­ing RNAs in breast cancer. Arch Iran Med 2016; 19(7): 508–517. doi: 0161907/AIM.0011.

4. Dianatpour A, Ghafouri-Fard S. The role of long non cod­­ing RNAs in the repair of DNA double strand breaks. Int J Mol Cell Med 2017; 6(1): 1–12.

5. Oliva-Rico D, Her­rera LA. Regulated expres­sion of the lncRNA TERRA and its impact on telomere bio­logy. Mech Age­­ing Dev 2017; 167: 16–23. doi: 10.1016/j.mad.2017.09.001.

6. Mowel WK, Kotzin JJ, McCright SJ et al. Control of im­mune cell homeostasis and function by lncRNAs. Trends Im­munol 2018; 39(1): 55–69. doi: 10.1016/j.it.2017.08.009.

7. Faramarzi S, Dianatpour A, Ghafouri-Fard S. Discover­­ing the role of long non-cod­­ing RNAs in regulation of steroid receptors signal­­ing in cancer. J Biol and Today’s World 2017; 6(12): 248–258. doi: 10.15412/J.JBTW.01061202.

8. Kornfeld JW, Brün­­ing JC. Regulation of metabolism by long, non-cod­­ing RNAs. Front Genet 2014; 5: 57. doi: 10.3389/fgene.2014.00057.

9. Iranpour M, Soudyab M, Geranpayeh L et al. Expres­sion analysis of four long noncod­­ing RNAs in breast cancer. Tumour Biol 2016; 37(3): 2933–2940. doi: 10.1007/s13277-015-4135-2.

10. Nikpayam E, Tashar­rofi B, Sar­rafzadeh S et al. The role of long non-cod­­ing RNAs in ovarian cancer. Iran Bio-med J 2017; 21(1): 3–15. doi: 10.6091/.21.1.24.

11. Nikpayam E, Soudyab M, Tashar­rofi B et al. Expres­sion analysis of long non-cod­­ing ATB and its putative target in breast cancer. Breast Dis 2017; 37(1):11–20. doi: 10.3233/BD-160264.

12. Taheri M, Omrani MD, Ghafouri-Fard S. Long non-cod­­ing RNAs expres­sion in renal cell carcinoma. J Biol Today’s World 2017; 6(12): 240–247. doi: 10.15412/J.JBTW.01061201.

13. Tashar­rofi B, Soudyab M, Nikpayam E et al. Comparative expres­sion analysis of hypoxia-inducible factor-alpha and its natural occur­r­­ing antisense in breast cancer tis­sues and adjacent noncancerous tis­sues. Cell Biochem Funct 2016; 34(8): 572–578. doi: 10.1002/cbf.3230.

14. Taheri M, Omrani MD, Ghafouri-Fard S. Long non-cod­­ing RNA expres­sion in bladder cancer. Biophys Rev 2017; 10(4): 1205–1213. doi: 10.1007/s12551-017-0379-y.

15. Taheri M, Habibi M, Noroozi R et al. HOTAIR genetic variants are as­sociated with prostate cancer and benign prostate hyperplasia in an Iranian population. Gene 2017; 613: 20–4. doi: 10.1016/j.gene.2017.02.031.

16. Taheri M, Pouresmaeili F, Omrani MD et al. As­sociation of ANRIL gene polymorphisms with prostate cancer and benign prostatic hyperplasia in an Iranian population. Biomark Med 2017; 11(5): 413–422. doi: 10.2217/bm­m-2016-0378.

17. Motevaseli E, Azam R, Akrami SM et al. The ef­fect of lactobacil­lus crispatus and lactobacil­lus rhamnosusculture supernatants on expres­sion of autophagy genes and HPV E6 and E7 oncogenes in the HeLa cell line. Cell J 2016; 17(4): 601–607.

18. Taherian-Esfahani Z, Abedin-Do A, Nouri Z et al. Lactobacil­li dif­ferential­ly modulate mTOR and Wnt/β-catenin pathways in dif­ferent cancer cell lines. Iran J Cancer Prev 2016; 9(3): e5369. doi: 10.17795/ijcp-5369.

19. Wang H, Zhao Y, Chen M et al. Identification of novel long non-cod­­ing and circular RNAs in human papil­lomavirus-mediated cervical cancer. Front Microbio­l 2017; 8: 1720. doi: 10.3389/fmicb.2017.01720.

20. Goedert L, Plaça JR, Nunes EM et al. Long noncod­­ing RNAs in HPV-induced oncogenesis. Adv Virol 2016; 6: 1. doi: 10.4137/ATV.S29816.

21. Jiang Y, Li Y, Fang S et al. The role of MALAT1 cor­relates with HPV in cervical cancer. Oncol Lett 2014; 7(6): 2135–2141. doi: 10.3892/ol.2014.1996.

22. Sun R, Qin C, Jiang B et al. Down-regulation of MALAT1 inhibits cervical cancer cell invasion and meta­stasis by inhibition of epithelial-mesenchymal transition. Mol Biosyst 2016; 12(3): 952–962. doi: 10.1039/c5mb00685f.

23. Sharma S, Mandal P, Sadhukhan T et al. Bridg­­ing links between long noncod­­ing RNA HOTAIR and HPV oncoprotein E7 in cervical cancer pathogenesis. Sci Rep 2015; 5: 11724. doi: 10.1038/srep11724.

24. Wang X, Wang Z, Wang J et al. LncRNA MEG3 has anti-activity ef­fects of cervical cancer. Biomed Pharmacother 2017; 94: 636–643. doi: 10.1016/j.bio­pha.2017.07.056.

25. Wen Q, Liu Y, Lyu H et al. Long noncod­­ing RNA GAS5, which acts as a tumor suppres­sor via microRNA 21, regulates cisplatin resistance expres­sion in cervical cancer. Int J Gynecol Cancer 2017; 27(6): 1096–1108. doi: 10.1097/IGC.0000000000001028.

26. Jin XJ, Chen XJ, Hu Y et al. LncRNA-TCONS_00026907 is involved in the progres­sion and prognosis of cervical cancer through inhibit­­ing miR-143-5p. Cancer Med 2017; 6(6): 1409–1423. doi: 10.1002/cam4.1084.

27. Sun G, Wang C, Zhang H. Long non-cod­­ing RNA XIST promotes cervical cancer cell epithelial-mesenchymal transition through the Wnt/beta-catenin pathway. Int J Clin Exp Pathol 2017; 10(2): 2333–2339.

28. Zhang J, Gao Y. CCAT-1 promotes proliferation and inhibits apoptosis of cervical cancer cel­ls via the Wnt signal­­ing pathway. Oncotarget 2017; 8(40): 68059–68070. doi: 10.18632/oncotarget.19155.

29. Lee M, Kim HJ, Kim SW et al. The long non-cod­­ing RNA HOTAIR increases tumour growth and invasion in cervical cancer by target­­ing the Notch pathway. Oncotarget 2016; 7(28): 44558–44571. doi: 10.18632/oncotarget.10065.

30. Kim HJ, Lee DW, Yim GW et al. Long non-cod­­ing RNA HOTAIR is as­sociated with human cervical cancer progres­sion. Int J Oncol 2015; 46(2): 521–30. doi: 10.3892/ijo.2014.2758.

31. Zheng P, Xiong Q, Wu Y et al. Quantitative proteomics analysis reveals novel insights into mechanisms of action of long noncod­­ing RNA hox transcript antisense intergenic RNA (HOTAIR) in HeLa Cel­ls. Mol Cell Proteomics 2015; 14(6): 1447–1463. doi: 10.1074/mcp.M114.043984.

32. Zhang L, Qian H, Sha M et al. Downregulation of HOTAIR expres­sion mediated anti-metastatic ef­fect of artesunate on cervical cancer by inhibit­­ing COX-2 expres­sion. PLoS One 2016; 11(10): e0164838. doi: 10.1371/journal.pone.

33. Peng L, Yuan X, Jiang B et al. LncRNAs: key players and novel insights into cervical cancer. Tumour Biol 2016; 37(3): 2779–2788. doi: 10.1007/s13277-015-4663-9.

34. Hu Y, Sun X, Mao C et al. Upregulation of long noncod­­ing RNA TUG1 promotes cervical cancer cell proliferation and migration. Cancer Med 2017; 6(2): 471–482. doi: 10.1002/cam4.994.

35. Kim HJ, Eoh KJ, Kim LK et al. The long noncod­­ing RNA HOXA11 antisense induces tumor progres­sion and stemness maintenance in cervical cancer. Oncotarget 2016; 7(50): 83001–83016. doi: 10.18632/oncotarget.12863.

36. Sun NX, Ye C, Zhao Q et al. Long noncod­­ing RNA-EBIC promotes tumor cell invasion by bind­­ing to EZH2 and repres­s­­ing E-cadherin in cervical cancer. PloS One 2014; 9(7): e100340. doi: 10.1371/journal.pone.0100340.

37. Sun J, Chu H, Ji J et al. Long non-cod­­ing RNA HOTAIR modulates HLA-G expres­sion by absorb­­ing miR-148a in human cervical cancer. Int J Oncol 2016; 49(3): 943–952. doi: 10.3892/ijo.2016.3589.

38. Bolha L, Ravnik-Glavac M, Glavac D. Long noncod­­ing RNAs as bio­markers in cancer. Dis Markers 2017; 2017: 7243968. doi: 10.1155/2017/7243968.

39. Zhang J, Yao T, Lin Z et al. Aber­rant methylation of MEG3 functions as a potential plasma-based bio­marker for cervical cancer. Sci Rep 2017; 7: 6271. doi: 10.1038/s41598-017-06502-7.

40. Campos-Par­ra AD, Padua-Bracho A, Pedroza-Tor­res A et al. Comprehensive transcriptome analysis identifies pathways with therapeutic potential in local­ly advanced cervical cancer. Gynecol Oncol 2016; 143(2): 406–413. doi: 10.1016/j.ygyno.2016.08.327.

Štítky
Dětská onkologie Chirurgie všeobecná Onkologie

Článek vyšel v časopise

Klinická onkologie

Číslo 6

2018 Číslo 6
Nejčtenější tento týden
Nejčtenější v tomto čísle
Kurzy Podcasty Doporučená témata Časopisy
Přihlášení
Zapomenuté heslo

Zadejte e-mailovou adresu, se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se

#ADS_BOTTOM_SCRIPTS#