Top

Journal of Cancer Research and Clinical Oncology

Published in:

01-04-2020 | Metastasis | Review – Cancer Research

MicroRNAs that regulate PTEN as potential biomarkers in colorectal cancer: a systematic review

Authors: Jianrong Liu, Fei Ke, Tingting Chen, Qing Zhou, Lingling Weng, Jiani Tan, Weixing Shen, Liu Li, Jinyong Zhou, Changliang Xu, Haibo Cheng, Jinrong Zhou

Published in: Journal of Cancer Research and Clinical Oncology | Issue 4/2020

Abstract

Purpose

MicroRNAs (miRNAs) participate in a variety of biological processes, including tumorigenesis, progression, invasion, and drug resistance to multiple cancers. Phosphatase and tensin homolog (PTEN) is a cancer suppressor gene that has been certified to be regulated by miRNAs in various tumors, including colorectal cancer (CRC). In this review, we screened articles focusing on low PTEN expression in CRC, observed the expression of related miRNAs, analyzed their correlation and relationship with clinicopathological features, and discussed the possibility of these miRNAs as prognostic molecules.

Methods

We conducted a systematic search for articles published in the Web of Science, PubMed and EBSCO databases between January 1, 2002, and July 18, 2019. We identified these studies by using combinations of the following index entries and key words: ‘colorectal tumor OR colorectal neoplasm OR colorectal carcinoma OR colorectal cancer OR CRC’, ‘protein tyrosine phosphatase OR PTEN’, and ‘microRNA OR MiRNA OR miRNA OR MicroRNA’. Moreover, we evaluated the underlying association between alterations in PTEN and CRC prognosis.

Results

PTEN expression was obviously lower in CRC tissues than in normal mucosa. However, PTEN expression did not differ significantly between adenoma and normal tissues. PTEN tends to be negatively associated with tumor size and metastasis. MiR-21, miR-200a, miR-543, miR-32, miR-92a, miR-26a, miR-106a and miR-181a were correlated with the downregulation of PTEN. MiR-26a, miR-106a and miR-181a were obviously higher in CRC tissues than in normal tissues, while PTEN was downregulated in CRC tissues. Additionally, miRNAs were mainly positively correlated with distant metastasis, followed by TNM stage. The relationship between miRNAs and tumor differentiation is controversial. However, there were no significant differences between miRNAs and either sex or age.

Conclusions

The loss of PTEN may be a diagnostic factor for CRC patients. The above-mentioned miRNAs may function as oncogenes in CRC and represent potential targets for CRC therapy. However, further prospective clinical studies are necessary.

Society, A.C. (2018) Survival rates for colorectal cancer, by stage. https://www.cancer.org/cancer/colon-rectal-cancer/detection-diagnosis-staging/survival-rates.Html

Arabsorkhi Z, Gharib E, Yaghmoorian Khojini J, Farhadieh ME, Nazemalhosseini-Mojarad E, Zali MR (2019) miR-298 plays a pivotal role in colon cancer invasiveness by targeting PTEN. J Cell Physiol. https://doi.org/10.1002/jcp.29310 CrossRefPubMed

Athanasiou T et al (2004) Off-pump myocardial revascularization is associated with less incidence of stroke in elderly patients. Ann Thorac Surg 77:745–753. https://doi.org/10.1016/j.athoracsur.2003.07.002 CrossRefPubMed

Bakirtzi K, Hatziapostolou M, Karagiannides I, Polytarchou C, Jaeger S, Iliopoulos D, Pothoulakis C (2011) Neurotensin signaling activates microRNAs-21 and -155 and Akt, promotes tumor growth in mice, and is increased in human colon tumors. Gastroenterology 141:1749–1761. https://doi.org/10.1053/j.gastro.2011.07.038 CrossRefPubMed

Berania I et al (2017) Four PTEN-targeting co-expressed miRNAs and ACTN4- targeting miR-548b are independent prognostic biomarkers in human squamous cell carcinoma of the oral tongue. Int J Cancer 141:2318–2328. https://doi.org/10.1002/ijc.30915 CrossRefPubMed

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424. https://doi.org/10.3322/caac.21492 CrossRefPubMed

Calin GA et al (2002) Frequent deletions and down-regulation of micro RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA 99:15524–15529. https://doi.org/10.1073/pnas.242606799 CrossRefPubMedPubMedCentral

Carthew RW, Sontheimer EJ (2009) Origins and mechanisms of miRNAs and siRNAs. Cell 136:642–655. https://doi.org/10.1016/j.cell.2009.01.035 CrossRefPubMedCentralPubMed

Coffer PJ, Jin J, Woodgett JR (1998) Protein kinase B (c-Akt): a multifunctional mediator of phosphatidylinositol 3-kinase activation. Biochem J 335(Pt 1):1–13. https://doi.org/10.1042/bj3350001 CrossRefPubMedCentralPubMed

Colakoglu T et al (2008) Clinicopathological significance of PTEN loss and the phosphoinositide 3-kinase/Akt pathway in sporadic colorectal neoplasms: is PTEN loss predictor of local recurrence? Am J Surg 195:719–725. https://doi.org/10.1016/j.amjsurg.2007.05.061 CrossRefPubMed

Coronel-Hernandez J et al (2019) Cell migration and proliferation are regulated by miR-26a in colorectal cancer via the PTEN-AKT axis. Cancer Cell Int 19:80. https://doi.org/10.1186/s12935-019-0802-5 CrossRefPubMedCentralPubMed

Cota GF, de Sousa MR, Fereguetti TO, Rabello A (2013) Efficacy of anti-leishmania therapy in visceral leishmaniasis among HIV infected patients: a systematic review with indirect comparison. PLoS Negl Trop Dis 7:e2195. https://doi.org/10.1371/journal.pntd.0002195 CrossRefPubMedCentralPubMed

De Guzman R, Malik M (2019) Global cancer burden and natural disasters: a focus on Asia’s vulnerability, resilience building, and impact on cancer care. J Glob Oncol 5:1–8. https://doi.org/10.1200/jgo.19.00037 CrossRefPubMed

Gomez-Espana MA et al (2019) SEOM clinical guidelines for diagnosis and treatment of metastatic colorectal cancer (2018). Clin Transl Oncol 21:46–54. https://doi.org/10.1007/s12094-018-02002-w CrossRefPubMed

Goswami CP, Nakshatri H (2014) PROGgeneV2: enhancements on the existing database. BMC Cancer. 14:970. https://doi.org/10.1186/1471-2407-14-970 CrossRefPubMedCentralPubMed

Hamid AA, Gray KP, Huang Y, Bowden M, Pomerantz M, Loda M, Sweeney CJ (2019) Loss of PTEN expression detected by fluorescence immunohistochemistry predicts lethal prostate cancer in men treated with prostatectomy. Eur urol oncol 2:475–482. https://doi.org/10.1016/j.euo.2018.09.003 CrossRefPubMed

Han S et al (2018) Association between Hypoxia-Inducible factor-2alpha (HIF-2alpha) expression and colorectal cancer and its prognostic role: a systematic analysis. Cell Physiol Biochem 48:516–527. https://doi.org/10.1159/000491806 CrossRefPubMed

Hollander MC, Blumenthal GM, Dennis PA (2011) PTEN loss in the continuum of common cancers, rare syndromes and mouse models. Nat Rev Cancer 11:289–301. https://doi.org/10.1038/nrc3037 CrossRefPubMedCentralPubMed

Jiang YA et al (2003) Expression and significance of PTEN, hypoxia-inducible factor-1 alpha in colorectal adenoma and adenocarcinoma. World J Gastroenterol 9:491–494. https://doi.org/10.3748/wjg.v9.i3.491 CrossRefPubMedCentralPubMed

Kechagioglou P et al (2014) Tumor suppressor PTEN in breast cancer: heterozygosity, mutations and protein expression. Anticancer Res 34:1387–1400PubMed

Ke TW, Wei PL, Yeh KT, Chen WT, Cheng YW (2015) MiR-92a promotes cell metastasis of colorectal cancer through PTEN-mediated PI3K/AKT pathway. Ann Surg Oncol 22:2649–2655. https://doi.org/10.1245/s10434-014-4305-2 CrossRefPubMed

Khalid A, Hussain T, Manzoor S, Saalim M, Khaliq S (2017) PTEN: a potential prognostic marker in virus-induced hepatocellular carcinoma. Tumour Biol 39:1010428317705754. https://doi.org/10.1177/1010428317705754 CrossRefPubMed

Kim MS, Lee J, Sidransky D (2010) DNA methylation markers in colorectal cancer. Cancer Metastasis Rev 29:181–206. https://doi.org/10.1007/s10555-010-9207-6 CrossRefPubMed

Li Y et al (2016a) MiR-200a acts as an oncogene in colorectal carcinoma by targeting PTEN. Exp Mol Pathol 101:308–313. https://doi.org/10.1016/j.yexmp.2016.10.006 CrossRefPubMed

Li Z, Wang H, Xu Z, Sun Y, Han J (2016b) Expression and mechanism of microRNA-181A on incidence and survival in late liver metastases of colorectal cancer. Oncol Rep 35:1403–1408. https://doi.org/10.3892/or.2016.4546 CrossRefPubMed

Li A, Qiu M, Zhou H, Wang T, Guo W (2017) PTEN, insulin resistance and cancer. Curr Pharm Des 23:3667–3676. https://doi.org/10.2174/1381612823666170704124611 CrossRefPubMed

Liang J et al (2015) Phosphatidylinositol 3-kinases pathway mediates lung caspase-1 activation and high mobility group box 1 production in a toluene-diisocyanate induced murine asthma model. Toxicol Lett 236:25–33. https://doi.org/10.1016/j.toxlet.2015.04.011 CrossRefPubMed

Liu P, Wang Z, Wei W (2014) Phosphorylation of Akt at the C-terminal tail triggers Akt activation. Cell cycle (Georgetown, Tex) 13:2162–2164. https://doi.org/10.4161/cc.29584 CrossRef

Lo CK, Mertz D, Loeb M (2014) Newcastle-Ottawa scale: comparing reviewers’ to authors’ assessments. BMC Med Res Methodol 14:45. https://doi.org/10.1186/1471-2288-14-45 CrossRefPubMedCentralPubMed

Macfarlane LA, Murphy PR (2010) MicroRNA: biogenesis, function and role in cancer. Curr Genomics 11:537–561. https://doi.org/10.2174/138920210793175895 CrossRefPubMedCentralPubMed

Malaney P, Uversky VN, Dave V (2017) PTEN proteoforms in biology and disease. CMLS 74:2783–2794. https://doi.org/10.1007/s00018-017-2500-6 CrossRefPubMed

Mandrik O, Ekwunife OI, Zielonke N, Meheus F, Severens JL, Lhachimi SK, Murillo R (2017) What determines the effects and costs of breast cancer screening? A protocol of a systematic review of reviews. Syst Rev 6:122. https://doi.org/10.1186/s13643-017-0510-y CrossRefPubMedCentralPubMed

Margulis AV et al (2014) Quality assessment of observational studies in a drug-safety systematic review, comparison of two tools: the Newcastle-Ottawa Scale and the RTI item bank. Clin Epidemiol 6:359–368. https://doi.org/10.2147/clep.s66677 CrossRefPubMedCentralPubMed

McGrath TA, Moher D, McInnes MDF (2019) Steps toward more complete reporting of systematic reviews of diagnostic test accuracy: preferred reporting items for systematic reviews and Meta-analyses of diagnostic test accuracy (PRISMA-DTA). Syst Rev 8:166. https://doi.org/10.1186/s13643-019-1090-9 CrossRefPubMedCentralPubMed

Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST, Patel T (2007) MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology 133:647–658. https://doi.org/10.1053/j.gastro.2007.05.022 CrossRefPubMed

Milella M et al (2015) PTEN: multiple functions in human malignant tumors. Front Oncol 5:24. https://doi.org/10.3389/fonc.2015.00024 CrossRefPubMedCentralPubMed

Molinari F, Frattini M (2013) Functions and regulation of the PTEN gene in colorectal cancer. Front Oncol 3:326. https://doi.org/10.3389/fonc.2013.00326 CrossRefPubMed

Piedade D, Azevedo-Pereira JM (2016) The Role of microRNAs in the pathogenesis of herpesvirus infection. Viruses. https://doi.org/10.3390/v8060156 CrossRefPubMedCentralPubMed

POPULATIONOF.NET (2019) Asia population

Qin Y, Huo Z, Song X, Chen X, Tian X, Wang X (2018) mir-106a regulates cell proliferation and apoptosis of colon cancer cells through targeting the PTEN/PI3K/AKT signaling pathway. Oncol Lett 15:3197–3201. https://doi.org/10.3892/ol.2017.7715 CrossRefPubMed

Saavedra L, Catarino R, Heinz T, Heilmann I, Bezanilla M, Malho R (2015) Phosphatase and tensin homolog is a growth repressor of both rhizoid and gametophore development in the moss physcomitrella patens. Plant Physiol 169:2572–2586. https://doi.org/10.1104/pp.15.01197 CrossRefPubMedCentralPubMed

Salmena L, Carracedo A, Pandolfi PP (2008) Tenets of PTEN tumor suppression. Cell 133:403–414. https://doi.org/10.1016/j.cell.2008.04.013 CrossRefPubMed

Shen H et al (2016) TGF-beta1 induces erlotinib resistance in non-small cell lung cancer by down-regulating PTEN. Biomed Pharmacother 77:1–6. https://doi.org/10.1016/j.biopha.2015.10.018 CrossRefPubMed

Stang A (2010) Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 25:603–605. https://doi.org/10.1007/s10654-010-9491-z CrossRefPubMed

Stefano S, Giovanni S (2019) The PTEN tumor suppressor gene in soft tissue sarcoma. Cancers. https://doi.org/10.3390/cancers11081169 CrossRefPubMedCentralPubMed

Sun J, Zhou J, Dong M, Sheng W (2017) Dysregulation of MicroRNA-543 expression in colorectal cancer promotes tumor migration and invasion. Mol Carcinog 56:250–257. https://doi.org/10.1002/mc.22489 CrossRefPubMed

Temraz S, Nassar F, Nasr R, Charafeddine M, Mukherji D, Shamseddine A (2019) Gut microbiome: a promising biomarker for immunotherapy in colorectal cancer. Int J Mol Sci. https://doi.org/10.3390/ijms20174155 CrossRefPubMedCentralPubMed

Thies KA, Lefler JE, Leone G, Ostrowski MC (2019) PTEN in the stroma. Cold Spring Harbor Perspect Med. https://doi.org/10.1101/cshperspect.a036111 CrossRef

Tian J, Yuan L (2018) Sirtuin 6 inhibits colon cancer progression by modulating PTEN/AKT signaling. Biomed Pharmacother 106:109–116. https://doi.org/10.1016/j.biopha.2018.06.070 CrossRefPubMed

Tian F, Jia L, Chu Z, Han H, Zhang Y, Cai J (2018) MicroRNA-519a inhibits the proliferation and promotes the apoptosis of ovarian cancer cells through targeting signal transducer and activator of transcription 3. Exp Ther Med 15:1819–1824. https://doi.org/10.3892/etm.2017.5600 CrossRefPubMed

Toiyama Y, Okugawa Y, Fleshman J, Richard Boland C, Goel A (2018) MicroRNAs as potential liquid biopsy biomarkers in colorectal cancer: a systematic review. Biochim Biophys Acta 1870:274–282. https://doi.org/10.1016/j.bbcan.2018.05.006 CrossRef

Vickers MM et al (2012) Stage-dependent differential expression of microRNAs in colorectal cancer: potential role as markers of metastatic disease. Clin Exp Metastasis 29:123–132. https://doi.org/10.1007/s10585-011-9435-3 CrossRefPubMed

Wang LL et al (2017) PTEN/PI3K/AKT protein expression is related to clinicopathological features and prognosis in breast cancer with axillary lymph node metastases. Hum Pathol 61:49–57. https://doi.org/10.1016/j.humpath.2016.07.040 CrossRefPubMed

Wang Q et al (2019) Long noncoding RNA Linc02023, and is regulates PTEN stability and suppresses tumorigenesis of colorectal cancer in a PTEN-dependent pathway. Cancer Lett 451:68–78. https://doi.org/10.1016/j.canlet.2019.02.041 CrossRefPubMed

Waniczek D et al (2013) PTEN expression profiles in colorectal adenocarcinoma and its precancerous lesions. Pol J Pathol 64:15–20CrossRefPubMed

Wise HM, Hermida MA, Leslie NR (2017) Prostate cancer, PI3K, PTEN and prognosis. Clin Sci (Lond) 131:197–210. https://doi.org/10.1042/cs20160026 CrossRef

Wu W et al (2013) The relationship between and clinical significance of MicroRNA-32 and phosphatase and tensin homologue expression in colorectal cancer. Genes Chromosomes Cancer 52:1133–1140. https://doi.org/10.1002/gcc.22108 CrossRefPubMed

Wu Y et al (2017) MicroRNA-21 (Mir-21) promotes cell growth and invasion by repressing tumor suppressor PTEN in colorectal cancer. Cell Physiol Biochem 43:945–958. https://doi.org/10.1159/000481648 CrossRefPubMed

Xie T, Huang M, Wang Y, Wang L, Chen C, Chu X (2016) MicroRNAs as regulators, biomarkers and therapeutic targets in the drug resistance of colorectal cancer. Cell Physiol Biochem 40:62–76. https://doi.org/10.1159/000452525 CrossRefPubMed

Xiong B, Cheng Y, Ma L, Zhang C (2013) MiR-21 regulates biological behavior through the PTEN/PI-3 K/Akt signaling pathway in human colorectal cancer cells. Int J Oncol 42:219–228. https://doi.org/10.3892/ijo.2012.1707 CrossRefPubMed

Xiong Y, Zhang YY, Wu YY, Wang XD, Wan LH, Li L, Zhou LM (2014) Correlation of over-expressions of miR-21 and Notch-1 in human colorectal cancer with clinical stages. Life Sci 106:19–24. https://doi.org/10.1016/j.lfs.2014.04.017 CrossRefPubMed

Xuan Y et al (2015) MicroRNAs in colorectal cancer: small molecules with big functions. Cancer Lett 360:89–105. https://doi.org/10.1016/j.canlet.2014.11.051 CrossRefPubMed

Yang Y, Yang JJ, Tao H, Jin WS (2015) MicroRNA-21 controls hTERT via PTEN in human colorectal cancer cell proliferation. J Physiol Biochem 71:59–68. https://doi.org/10.1007/s13105-015-0380-5 CrossRefPubMed

Yazdani Y, Farazmandfar T, Azadeh H, Zekavatian Z (2016) The prognostic effect of PTEN expression status in colorectal cancer development and evaluation of factors affecting it: miR-21 and promoter methylation. J Biomed Sci 23:9. https://doi.org/10.1186/s12929-016-0228-5 CrossRefPubMedCentralPubMed

Zaheer U, Faheem M, Qadri I, Begum N, Yassine HM, Al Thani AA, Mathew S (2019) Expression profile of MicroRNA: an emerging hallmark of Cancer. Curr Pharm Des 25:642–653. https://doi.org/10.2174/1386207322666190325122821 CrossRefPubMed

Zhang JG, Wang JJ, Zhao F, Liu Q, Jiang K, Yang GH (2010) MicroRNA-21 (miR-21) represses tumor suppressor PTEN and promotes growth and invasion in non-small cell lung cancer (NSCLC). Clin Chim Acta 411:846–852. https://doi.org/10.1016/j.cca.2010.02.074 CrossRefPubMed

Zhang G, Zhou H, Xiao H, Liu Z, Tian H, Zhou T (2014) MicroRNA-92a functions as an oncogene in colorectal cancer by targeting PTEN. Dig Dis Sci 59:98–107. https://doi.org/10.1007/s10620-013-2858-8 CrossRefPubMed

Zhang H, Liu A, Feng X, Tian L, Bo W, Wang H, Hu Y (2017) MiR-132 promotes the proliferation, invasion and migration of human pancreatic carcinoma by inhibition of the tumor suppressor gene PTEN. Prog Biophys Mol Biol. https://doi.org/10.1016/j.pbiomolbio.2017.09.019 CrossRefPubMedCentralPubMed

Title: MicroRNAs that regulate PTEN as potential biomarkers in colorectal cancer: a systematic review
Authors: Jianrong Liu
Fei Ke
Tingting Chen
Qing Zhou
Lingling Weng
Jiani Tan
Weixing Shen
Liu Li
Jinyong Zhou
Changliang Xu
Haibo Cheng
Jinrong Zhou
Publication date: 01-04-2020
Publisher: Springer Berlin Heidelberg
Keywords: Metastasis
Colorectal Cancer
Colorectal Cancer
Biomarkers
Published in: Journal of Cancer Research and Clinical Oncology / Issue 4/2020
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-020-03172-3

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

MicroRNAs that regulate PTEN as potential biomarkers in colorectal cancer: a systematic review

Abstract

Purpose

Methods

Results

Conclusions

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 4/2020

Correction to: Restoration of MARCKS enhances chemosensitivity in cancer

Myeloid sarcoma is associated with poor clinical outcome in pediatric patients with acute myeloid leukemia

Predictors of survival and recurrence after primary surgery for cervical metastasis of unknown primary

Long-term outcome of patients with intermediate- and high-risk endometrial cancer after pelvic and paraaortic lymph node dissection: a comparison of laparoscopic vs. open procedure

An increased bone mineral density is an adverse prognostic factor in patients with systemic mastocytosis

Treatment patterns and survival after 18F-fluorodeoxyglucose positron emission tomography/computed tomography-guided local consolidation therapy for oligometastatic non-small cell lung cancer: a two-center propensity score-matched analysis

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page