The Promising Signatures of Circulating microRNA-145 in Epithelial Ovarian Cancer Patients

Author(s): Mariyam Zuberi, Rashid Mir, Imran Khan, Jamsheed Javid, Sameer Ahmad Guru, Musadiq Bhat, Mamta Pervin Sumi, Imtiyaz Ahmad, Mirza Masroor, Prasant Yadav, Sreenivas Vishnubhatla, Alpana Saxena*

Journal Name: MicroRNA

Volume 9 , Issue 1 , 2020

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Background: Epithelial ovarian cancer continues to be a deleterious threat to women as it is asymptomatic and is typically detected in advanced stages. Cogent non-invasive biomarkers are therefore needed which are effective in apprehending the disease in early stages. Recently, miRNA deregulation has shown a promising magnitude in ovarian cancer tumorigenesis. miRNA-145(miR- 145) is beginning to be understood for its possible role in cancer development and progression. In this study, we identified the clinicopathological hallmarks altered owing to the downexpression of serum miR-145 in EOC.

Methods: 70 serum samples from histopathologically confirmed EOC patients and 70 controls were collected. Total RNA from serum was isolated by Trizol method, polyadenylated and reverse transcribed into cDNA. Expression level of miR-145 was detected by miRNA qRT-PCR using RNU6B snRNA as reference.

Results: The alliance of miR-145 profiling amongst patients and controls established itself to be conspicuous with a significant p-value (p<0.0001). A positive conglomeration (p=0.04) of miR-145 profiling was manifested with histopathological grade. Receiver Operating Characteristic (ROC) curve highlights the diagnostic potential and makes it imminent with a robust Area Under the curve (AUC). A positive correlation with the ROC curve was also noted for histological grade, FIGO stage, distant metastasis, lymph node status and survival.

Conclusion: Our results propose that miR-145 down-regulation might be a possible touchstone for disease progression and be identified as a diagnostic marker and predict disease outcome in EOC patients.

Keywords: Circulating miRNAs, clinicopathological, diagnosis, prognosis, ROC, non-invasive.

Cho A, Howell VM, Colvin EK. The extracellular matrix in epithelial ovarian cancer - A piece of a puzzle. Front Oncol 2015; 5: 245.
Ha TY. MicroRNAs in human diseases: from cancer to cardiovascular disease. Immune Netw 2011; 11(3): 135-54.
Vychytilova-Faltejskova P, Slaby O. Circulating blood-borne micrornas as biomarkers in solid tumors. Exp Suppl 2015; 106: 75-122.
Kim TH, Song JY, Park H, et al. miR-145, targeting high-mobility group A2, is a powerful predictor of patient outcome in ovarian carcinoma. Cancer Lett 2015; 28; 356[2 Pt B]: 937-45.
Liang H, Jiang Z, Xie G, Lu Y. Serum microRNA-145 as a novel biomarker in human ovarian cancer. Tumor Biol J Int Soc Oncodevelop Biol Med 2015; 36(7): 5305-13.
Dong R, Liu X, Zhang Q, et al. miR-145 inhibits tumor growth and metastasis by targeting metadherin in high-grade serous ovarian carcinoma. Oncotarget 2014; 5(21): 10816-29.
Zhu X, Li Y, Xie C, et al. miR-145 sensitizes ovarian cancer cells to paclitaxel by targeting Sp1 and Cdk6. Int J Cancer J Int Cancer 2014; 135(6): 1286-96.
Ding W, Tan H, Zhao C, et al. MiR-145 suppresses cell proliferation and motility by inhibiting ROCK1 in hepatocellular carcinoma. Tumour Biol 2016; 37(5): 6255-60.
Akao Y, Nakagawa Y, Naoe T. MicroRNA-143 and -145 in colon cancer. DNA Cell Biol 2007; 26(5): 311-20.
Akao Y, Nakagawa Y, Naoe T. MicroRNAs 143 and 145 are possible common onco-microRNAs in human cancers. Oncol Rep 2006; 16(4): 845-50.
Xu X, Wu X, Jiang Q, et al. Downregulation of microRNA-1 and microRNA-145 contributes synergistically to the development of colon cancer. Int J Mol Med 2015; 36(6): 1630-8.
Odenthal M, Hee J, Gockel I, et al. Serum microRNA profiles as prognostic/predictive markers in the multimodality therapy of locally advanced adenocarcinomas of the gastroesophageal junction. Int J Cancer 2015; 137(1): 230-7.
Zuberi M, Mir R, Das J, et al. Expression of serum miR-200a, miR-200b, and miR-200c as candidate biomarkers in epithelial ovarian cancer and their association with clinicopathological features. Clin Transl Oncol 2015; 17(10): 779-87.
Zuberi M, Khan I, Gandhi G, Ray PC, Saxena A. The conglomeration of diagnostic, prognostic and therapeutic potential of serum miR-199a and its association with clinicopathological features in epithelial ovarian cancer. Tumour Biol 2016; 37(8): 11259-66.
Zuberi M, Khan I, Mir R, Gandhi G, Ray PC, Saxena A. Utility of serum miR-125b as a diagnostic and prognostic indicator and its alliance with a panel of tumor suppressor genes in epithelial ovarian cancer. PLoS One 2016; 11(4): e0153902.
Sim JA, Abdul RK, Yi KJ, Chung M, et al. High microRNA-370 expression correlates with tumor progression and poor prognosis in breast cancer. J Breast Cancer 2015; 18(4): 323-8.
Bertoli G, Cava C, Castiglioni I. MicroRNAs: new biomarkers for diagnosis, prognosis, therapy prediction and therapeutic tools for breast cancer. Theranostics 2015; 5(10): 1122-43.
Eissa S, Matboli M, Sharawy A, El-Sharkawi F. Prognostic and biological significance of microRNA-221 in breast cancer. Gene 2015; 574(1): 163-7.
Vescovo VD, Denti MA. microRNA and lung cancer. Adv Exp Med Biol 2015; 889: 153-77.
Li W, Wang Y, Zhang Q, et al. MicroRNA-486 as a biomarker for early diagnosis and recurrence of non-small cell lung cancer. PLoS One 2015; 10(8)e0134220 [doi: 10.1371/journal.pone.0134220].
Khan MA, Zubair H, Srivastava SK, Singh S, Singh AP. Insights into the role of microRNAs in pancreatic cancer pathogenesis: potential for diagnosis, prognosis, and therapy. Adv Exp Med Biol 2015; 889: 71-87.
Paik WH, Song BJ, Kim HW, Kim HR, Hwang JH. MicroRNA-200c as a prognostic biomarker for pancreatic cancer. Korean J Gastroenterol 2015; 66(4): 215-20.
Zhao Y, Liu X, Zhong L, et al. The combined use of miRNAs and mRNAs as biomarkers for the diagnosis of papillary thyroid carcinoma. Int J Mol Med 2015; 36(4): 1097-103.
Sondermann A, Andreghetto FM, Moulatlet ACB, et al. MiR-9 and miR-21 as prognostic biomarkers for recurrence in papillary thyroid cancer. Clin Exp Metastasis 2015; 32(6): 521-30.
Ress AL, Perakis S, Pichler M. microRNAs and colorectal cancer. Adv Exp Med Biol 2015; 889: 89-103.
Thomas J, Ohtsuka M, Pichler M, Ling H. MicroRNAs: clinical relevance in colorectal cancer. Int J Mol Sci 2015; 16(12): 28063-76.
Sun X, Zhang S, Ma X. Prognostic value of microRNA-125 in various human malignant neoplasms: a meta-analysis. Clin Lab 2015; 61(11): 1667-74.
Miles GD, Seiler M, Rodriguez L, Rajagopal G, Bhanot G. Identifying microRNA/mRNA dysregulations in ovarian cancer. BMC Res Notes 2012; 5: 164. [doi: 10.1186/1756-0500-5-164].
Chen Z, Zeng H, Guo Y, et al. miRNA-145 inhibits non-small cell lung cancer cell proliferation by targeting c-Myc. J Exp Clin Cancer Res 2010; 29: 151.
Zhang Y, Yang X, Wu H, Zhou W, Liu Z. MicroRNA-145 inhibits migration and invasion via inhibition of fascin 1 protein expression in non-small-cell lung cancer cells. Mol Med Rep 2015; 12(4): 6193-8.
Kliese N, Gobrecht P, Pachow D, et al. miRNA-145 is downregulated in atypical and anaplastic meningiomas and negatively regulates motility and proliferation of meningioma cells. Oncogene 2013; 32(39): 4712-20.
Zheng L, Pu J, Qi T, et al. miRNA-145 targets v-ets erythroblastosis virus E26 oncogene homolog 1 to suppress the invasion, metastasis, and angiogenesis of gastric cancer cells. Mol Cancer Res 2013; 11(2): 182-93.
Pal A, Melling G, Hinsley EE, et al. Cigarette smoke condensate promotes pro-tumorigenic stromal-epithelial interactions by suppressing miR-145. J Oral Pathol Med 2013; 42(4): 309-14.
Noguchi S, Mori T, Hoshino Y, et al. Comparative study of anti-oncogenic microRNA-145 in canine and human malignant melanoma. J Vet Med Sci 2012; 74(1): 1-8.
Yang C, Wei W. The miRNA expression profile of the uveal melanoma. Sci China Life Sci 2011; 54(4): 351-8.
Blick C, Ramachandran A, McCormick R, et al. Identification of a hypoxia-regulated miRNA signature in bladder cancer and a role for miR-145 in hypoxia-dependent apoptosis. Br J Cancer 2015; 113(4): 634-44.
Qin J, Wang F, Jiang H, Xu J, Jiang Y, Wang Z. MicroRNA-145 suppresses cell migration and invasion by targeting paxillin in human colorectal cancer cells. Int J Clin Exp Pathol 2015; 8(2): 1328-40.
Yu Y, Nangia-Makker P, Farhana L, Rajendra GS, Levi E, Majumdar AP. miR-21 and miR-145 cooperation in regulation of colon cancer stem cells. Mol Cancer 2015; 14: 98.
Li MY, Hu XX. Meta-analysis of microRNA expression profiling studies in human cervical cancer. Med Oncol 2015; 32(6): 510.
Ramzy I, Hasaballah M, Marzaban R, Shaker O, Soliman ZA. Evaluation of microRNAs-29a, 92a and 145 in colorectal carcinoma as candidate diagnostic markers: an Egyptian pilot study. Clin Res Hepatol Gastroenterol 2015; 39(4): 508-15.
Wang C, Tao W, Ni S, et al. Tumor-suppressive microRNA-145 induces growth arrest by targeting SENP1 in human prostate cancer cells. Cancer Sci 2015; 106(4): 375-82.
Zheng H, Liu Z, Liu T, et al. Fas signaling promotes chemoresistance in gastrointestinal cancer by up-regulating P-glycoprotein. Oncotarget 2014; 5(21): 10763-77.
Yuan W, Sui C, Liu Q, Tang W, An H, Ma J. Up-regulation of microRNA-145 associates with lymph node metastasis in colorectal cancer. PLoS One 2014; 9(7)e102017
Tsikitis VL, White I, Mori M, et al. Differential expression of microRNA-320a, -145, and -192 along the continuum of normal mucosa to high-grade dysplastic adenomas of the colorectum. Am J Surg 2014; 207(5): 717-22.
Shi L, Wang Z, Sun G, Wan Y, Guo J, Fu X. miR-145 inhibits migration and invasion of glioma stem cells by targeting ABCG2. Neuromolecular Med 2014; 16(2): 517-28.
Chen X, Dong C, Law PTY, et al. MicroRNA-145 targets TRIM2 and exerts tumor-suppressing functions in epithelial ovarian cancer. Gynecol Oncol 2015; 139(3): 513-9.
Wang L, Wang B, Fang M, Guo F, Cui M. Identification of microRNAs and target genes involved in serous ovarian carcinoma and their influence on survival. Eur J Gynaecol Oncol 2014; 35(6): 655-61.
Wu H, Xiao Z, Wang K, Liu W, Hao Q. MiR-145 is downregulated in human ovarian cancer and modulates cell growth and invasion by targeting p70S6K1 and MUC1. Biochem Biophys Res Commun 2013; 441(4): 693-700.
Zhang W, Wang Q, Yu M, Wu N, Wang H. MicroRNA-145 function as a cell growth repressor by directly targeting c-Myc in human ovarian cancer. Technol Cancer Res Treat 2014; 13(2): 161-8.
Chung YW, Bae HS, Song JY, et al. Detection of microRNA as novel biomarkers of epithelial ovarian cancer from the serum of ovarian cancer patients. Int J Gynecol Cancer 2013; 23(4): 673-9.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2020
Published on: 17 February, 2020
Page: [49 - 57]
Pages: 9
DOI: 10.2174/2211536608666190225111234
Price: $65

Article Metrics

PDF: 11