Circulatory miRNA-155, miRNA-21 target PTEN expression and activity as a factor in breast cancer development

Saman Abdulrahman Ali; Zirak Faqia Ahmed Abdulrahman; Hemin Nasradeen Faraidun

doi:10.14715/cmb/2020.66.7.8

Issue

Vol. 66 No. 7: Issue 7

Issue Published : November 9, 2020

The undersigned hereby assign all rights, included but not limited to copyright, for this manuscript to CMB Association upon its submission for consideration to publication on Cellular and Molecular Biology. The rights assigned include, but are not limited to, the sole and exclusive rights to license, sell, subsequently assign, derive, distribute, display and reproduce this manuscript, in whole or in part, in any format, electronic or otherwise, including those in existence at the time this agreement was signed. The authors hereby warrant that they have not granted or assigned, and shall not grant or assign, the aforementioned rights to any other person, firm, organization, or other entity. All rights are automatically restored to authors if this manuscript is not accepted for publication.

Circulatory miRNA-155, miRNA-21 target PTEN expression and activity as a factor in breast cancer development

https://doi.org/10.14715/cmb/2020.66.7.8

Saman Abdulrahman Ali

Department of Biology, Salahaddin University-Erbil, Erbil,Kurdistan Region-Iraq

Zirak Faqia Ahmed Abdulrahman

Department of Biology, Salahaddin University-Erbil, Erbil, Kurdistan Region-Iraq

Hemin Nasradeen Faraidun

Department of Biology, University of Freiburg, Germany

Corresponding Author(s) : Saman Abdulrahman Ali

samanshwany8@raparinuni.org

Cellular and Molecular Biology, Vol. 66 No. 7: Issue 7
Article Published : October 31, 2020

Abstract

Breast cancer is a complex disease with multiple factors involved in its pathophysiological development. genetic mutations of BRCA1, BRCA2 and p53 are among the most well-studied factors. The role of other genetic factors like altered expression profiles, SNPs in the regulatory regions of different genes or epigenetic factors like promoter methylation and histone modifications are also well studied but no solid understanding is available on distinct key players triggering malignancy in breast cancer, (Phosphatase and tensin homolog) PTEN is known to be a crucial tumor suppressor as it has been reported to be missing or abnormally expressed in many cancer cells. Here in this were studied how PTEN is expressed in malignant and benign cancer cells by investigating its expression profile and cellular location using Immuno-fluorescence microscopy. At the same time, quantitative studies of the circulatory mi-RNAs related to the downregulation of PTEN, namely mir-21 and mir-155 have studied also. Sixty biopsy samples, forty were diagnosed to be malignant and twenty were benign. It has been found that PTEN is normally expressed in benign samples and its normally localized in the cell membrane, while in malignant samples the expression level of PTEN is lower or absent and it is translocated to the cytoplasm. Interestingly the quantitative expression of circulatory mir-21 and mir-155 in the blood plasma of the corresponding patients showed a related pattern with higher expression in malignant samples, therefore can it's clear that PTEN is in the cross-talk of genetics and epigenetic regulation in regard of the development of malignant breast cancer. At the same time, this study confirms the importance of circulatory miRNAs as a biomarker for early breast cancer detection.

Keywords

Breast cancer Immuno-fluorescence assay RNA Expression PTEN mir-21 and mir-155

Ali, S. A., Abdulrahman, Z. F. A., & Faraidun, H. N. (2020). Circulatory miRNA-155, miRNA-21 target PTEN expression and activity as a factor in breast cancer development. Cellular and Molecular Biology, 66(7), 44–50. https://doi.org/10.14715/cmb/2020.66.7.8

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References

Irene Foster. Cancer: A cell cycle defect. Radiography, 2008; 14(2):144–149.
Windows NT kernel description. https://www.breastcancer.org/symptoms/understandbc/statistics. A 2010 âˆ’ 09 – 30
Sahai E. Mechanisms of cancer cell invasion. Curr Opin Genet Dev 2005; (1):87-96.
Ahmed M, Rahman N. ATM and breast cancer susceptibility. Oncogene. 2006; 25(43):5906-11.
Muhammad Akram, Mehwish Iqbal, Muhammad Daniyal, and Asmat Ul- lah Khan. Awareness and current knowledge of breast cancer. Biol Res 2017; 50(1):33.
Asia Asiaf, Shiekh Tanveer Ahmad, Wani Arjumand, and Mohammad Afzal Zargar. MicroRNAs in breast cancer: diagnostic and therapeutic potential. Micro RNA and Cancer 2018; 23–43. Springer.
Recep Bayraktar and Katrien Van Roosbroeck. mir-155 in cancer drug resistance and as the target for miRNA-based therapeutics. Cancer and Metastasis Reviews 2018; 37(1):33–44.
Angela Bononi and Paolo Pinton. Study of pten subcellular localization. Methods 2015; 77:92–103.
Ong Wang, Zhiqiang Yin, Lingxiang Liu, Wen Gao, Wei Li, Yongqian Shu, and Jiali Xu. Second primary lung cancer after breast cancer: a population- based study of 6,269 women. Front Oncol 2018; 8:427.
Hu Y, Xu S, Jin W, Yi Q, Wei W. Effect of the PTEN gene on adhesion, invasion and metastasis of osteosarcoma cells. Oncol Rep. 2014; 32(4):1741-7.
Steven A Narod and Leonardo Salmena. Brca1 and brca2 mutations and breast cancer. Discov Med 2011; 12(66):445–453.
Leslie NR, Downes CP. PTEN function: how normal cells control it and tumour cells lose it. Biochem J 2004; 15;382(Pt 1):1-11.
Chalhoub N, Baker SJ. PTEN and the PI3-kinase pathway in cancer. Annu Rev Pathol. 2009; 4:127-50.
Giovanni Corso, Mattia Intra, Chiara Trentin, Paolo Veronesi, and Viviana Galimberti. Cdh1 germline mutations and hereditary lobular breast cancer. Fam Cancer 2016; 15(2):215–219.
Alexis Desrichard, Yannick Bidet, Nancy Uhrhammer, and Yves-Jean Bignon. Chek2 contribution to hereditary breast cancer in non-brca families. Breast Cancer Res 2011; 13(6): R119.
Sudipto Das, Jack E Dixon, and Wonhwa Cho. Membrane-binding and activation mechanism of pten. Proc Natl Acad Sci 2003; 100(13):7491–7496.
Liang-Ping Weng, Jessica L Brown, and Charis Eng. Pten induces apoptosis and cell cycle arrest through phosphoinositol-3-kinase/akt-dependent and- independent pathways. Hum Mol Genet 2001; 10(3):237–242.
Zuohe Song, Negin Saghafi, Vijay Gokhale, Marc Brabant, and Em- manuelle J Meuillet. Regulation of the activity of the tumor suppressor pten < thioredoxin in drosophila melanogaster. Exper Cell Res 2007; 313(6):1161–1171.
Amanda Gammon, Kory Jasperson, and Marjan Champine. Genetic basis of Cowden syndrome and its implications for clinical practice and risk management. Appl Clin Genet 2016; 9:83
Francien H van Nederveen, Aurel Perren, Hilde Dannenberg, B-J Petri, Winand NM Dinjens, Paul Komminoth, and Ronald R de Krijger. Pten gene loss, but not mutation, in benign and malignant phaeochromocytomas. J Pathol 2006; 209(2):274–280.
Hui Ling, Muller Fabbri, and George A. Calin. MicroRNAs and other non- coding RNAs as targets for anticancer drug development. Nat Rev Drug disco 2013; 12(11):847.
Scott M Hammond. An overview of microRNAs. Adv Drug Deliv Rev 2015; 87:3–14.
Nicole Ludwig, Petra Leidinger, Kurt Becker, Christina Backes, Tobias Fehlmann, Christian Pallasch, Steffi Rheinheimer, Benjamin Meder, Cord St¨ahler, Eckart Meese, et al. Distribution of mirna expression across human tissues. Nucleic Acids Res 2016; 44(8):3865–3877.
Tim Kehl, Christina Backes, Fabian Kern, Tobias Fehlmann, Nicole Lud- wig, Eckart Meese, Hans-Peter Lenhof, and Andreas Keller. About MicroRNAs, MicroRNA seeds, target genes and target pathways. Oncotarget 2017; 8(63):107167.
Andrea Ventura and Tyler Jacks. MicroRNAs and cancer: short RNAs go a long way. Cell 2009; 136(4):586–591.
Motoharu Ono, Kayo Yamada, Fabio Avolio, Vackar Afzal, Dalila Ben- Saddek, and Angus I Lamond. Targeted knock-down of mir21 primary transcripts using snomen vectors induces apoptosis in human cancer cell lines. PLoS One 2015; 10(9).
Fanyin Meng, Roger Henson, Hania Wehbe-Janek, Kalpana Ghoshal, Sam- son T Jacob, and Tushar Patel. MicroRNA-21 regulates expression of the pten tumor suppressor gene in human hepatocellular cancer. J Gastroenterol 2007; 133(2):647–658.
Longjiang Xu, Hong Leng, Xin Shi, Jiang Ji, and Jinxiang Fu. Mir-155 promotes cell proliferation and inhibits apoptosis by pten signaling pathway in the psoriasis. Biomed Pharma 2017; 90:524–530.
Masato Yasui, Satomi Matsuoka, and Masahiro Ueda. Pten hopping on the cell membrane is regulated via a positively-charged c2 domain. PLoS Comput Biol 2014; 10(9).
Nguyen HN, Afkari Y, Senoo H, Sesaki H, Devreotes PN, Iijima M. Mechanism of human PTEN localization revealed by heterologous expression in Dictyostelium. Oncogene 2014; 33(50):5688-96.
CB Knobbe, V Lapin, A Suzuki, and TW Mak. The roles of pten in development, physiology and tumorigenesis in mouse models: a tissue-by- tissue survey. Oncogene 2008; 27(41):5398–5415.
Ji-Hyun Chung and Charis Eng. Nuclear-cytoplasmic partitioning of phosphatase and tensin homologue deleted on chromosome 10 (pten) differentially regulates the cell cycle and apoptosis. Cancer Res 2005; 65(18):8096– 8100.
Helga B Salvesen, Ingunn Stefansson, May Britt Kalvenes, Soma Das, and Lars A Akslen. Loss of pten expression is associated with metastatic disease in patients with endometrial carcinoma. Cancer 2002; 94(8):2185–2191.
Jieli Li, Elaine J Tanhehco, and Brenda Russell. Actin dynamics is rapidly regulated by the pten and pip2 signaling pathways leading to myocyte hypertrophy. Am J Physiol-Heart Circ Physiol 2014; 307(11): H1618–H1625.
Ruedi Meili, Atsuo T Sasaki, and Richard A Firtel. Rho rocks pten. Nat cell biol 2005; 7(4):334.
Futoshi Teranishi, Naoko Takahashi, Nan Gao, Yoshimi Akamo, Hiromitsu Takeyama, Tadao Manabe, and Takashi Okamoto. Phosphoinositide 3- kinase inhibitor (wortmannin) inhibits pancreatic cancer cell motility and migration induced by hyaluronan in vitro and peritoneal metastasis in vivo. Cancer Sci 2009; 100(4):770–777.
Charlotte Glinge, Sebastian Clauss, Kim Boddum, Reza Jabbari, Javad Jabbari, Bjarke Risgaard, Philipp Tomsits, Bianca Hildebrand, Stefan K¨a¨ab, Reza Wakili, et al. Stability of circulating blood-based microRNAs– pre-analytic methodological considerations. PloS one 2017; 12(2).
Zhang P, Wu W, Chen Q, Chen M. Non-Coding RNAs and their Integrated Networks. J Integr Bioinform. 2019; 16(3).
Hongxing Zhou and Xuming Zhu. MicroRNA-21 and microRNA-30c as diagnostic biomarkers for prostate cancer: a meta-analysis. Cancer Manag Res 2019; 11:2039.
Ionut Negoi, Sorin Hostiuc, Massimo Sartelli, Ruxandra Irina Negoi, and Mircea Beuran. MicroRNA-21 as a prognostic biomarker in patients with pancreatic cancer–a systematic review and meta-analysis. Am J Surg 2017; 214(3):515–524.
Faraoni I, Antonetti FR, Cardone J, Bonmassar E. miR-155 gene: a typical multifunctional microRNA. Biochim Biophys Acta. 2009; 1792(6):497-505.
Fu, Y., Karstensen, J., and Brandt, P.: On the meridional geostrophic transport in the tropical Atlantic, Ocean Sci. 2017; 13, 531–549.
Kia V, Paryan M, Mortazavi Y, Biglari A, Mohammadi-Yeganeh S. Evaluation of exosomal miR-9 and miR-155 targeting PTEN and DUSP14 in highly metastatic breast cancer and their effect on low metastatic cells. J Cell Biochem 2019; 120(4):5666-5676.
Bordbar M, Darvishzadeh R, Pazhouhandeh M, Kahrizi D. An overview of genome editing methods based on endonucleases. Modern Genetics J 2020; 15(2): 75-92.

References

Irene Foster. Cancer: A cell cycle defect. Radiography, 2008; 14(2):144–149.

Windows NT kernel description. https://www.breastcancer.org/symptoms/understandbc/statistics. A 2010 âˆ’ 09 – 30

Sahai E. Mechanisms of cancer cell invasion. Curr Opin Genet Dev 2005; (1):87-96.

Ahmed M, Rahman N. ATM and breast cancer susceptibility. Oncogene. 2006; 25(43):5906-11.

Muhammad Akram, Mehwish Iqbal, Muhammad Daniyal, and Asmat Ul- lah Khan. Awareness and current knowledge of breast cancer. Biol Res 2017; 50(1):33.

Asia Asiaf, Shiekh Tanveer Ahmad, Wani Arjumand, and Mohammad Afzal Zargar. MicroRNAs in breast cancer: diagnostic and therapeutic potential. Micro RNA and Cancer 2018; 23–43. Springer.

Recep Bayraktar and Katrien Van Roosbroeck. mir-155 in cancer drug resistance and as the target for miRNA-based therapeutics. Cancer and Metastasis Reviews 2018; 37(1):33–44.

Angela Bononi and Paolo Pinton. Study of pten subcellular localization. Methods 2015; 77:92–103.

Ong Wang, Zhiqiang Yin, Lingxiang Liu, Wen Gao, Wei Li, Yongqian Shu, and Jiali Xu. Second primary lung cancer after breast cancer: a population- based study of 6,269 women. Front Oncol 2018; 8:427.

Hu Y, Xu S, Jin W, Yi Q, Wei W. Effect of the PTEN gene on adhesion, invasion and metastasis of osteosarcoma cells. Oncol Rep. 2014; 32(4):1741-7.

Steven A Narod and Leonardo Salmena. Brca1 and brca2 mutations and breast cancer. Discov Med 2011; 12(66):445–453.

Leslie NR, Downes CP. PTEN function: how normal cells control it and tumour cells lose it. Biochem J 2004; 15;382(Pt 1):1-11.

Chalhoub N, Baker SJ. PTEN and the PI3-kinase pathway in cancer. Annu Rev Pathol. 2009; 4:127-50.

Giovanni Corso, Mattia Intra, Chiara Trentin, Paolo Veronesi, and Viviana Galimberti. Cdh1 germline mutations and hereditary lobular breast cancer. Fam Cancer 2016; 15(2):215–219.

Alexis Desrichard, Yannick Bidet, Nancy Uhrhammer, and Yves-Jean Bignon. Chek2 contribution to hereditary breast cancer in non-brca families. Breast Cancer Res 2011; 13(6): R119.

Sudipto Das, Jack E Dixon, and Wonhwa Cho. Membrane-binding and activation mechanism of pten. Proc Natl Acad Sci 2003; 100(13):7491–7496.

Liang-Ping Weng, Jessica L Brown, and Charis Eng. Pten induces apoptosis and cell cycle arrest through phosphoinositol-3-kinase/akt-dependent and- independent pathways. Hum Mol Genet 2001; 10(3):237–242.

Zuohe Song, Negin Saghafi, Vijay Gokhale, Marc Brabant, and Em- manuelle J Meuillet. Regulation of the activity of the tumor suppressor pten < thioredoxin in drosophila melanogaster. Exper Cell Res 2007; 313(6):1161–1171.

Amanda Gammon, Kory Jasperson, and Marjan Champine. Genetic basis of Cowden syndrome and its implications for clinical practice and risk management. Appl Clin Genet 2016; 9:83

Francien H van Nederveen, Aurel Perren, Hilde Dannenberg, B-J Petri, Winand NM Dinjens, Paul Komminoth, and Ronald R de Krijger. Pten gene loss, but not mutation, in benign and malignant phaeochromocytomas. J Pathol 2006; 209(2):274–280.

Hui Ling, Muller Fabbri, and George A. Calin. MicroRNAs and other non- coding RNAs as targets for anticancer drug development. Nat Rev Drug disco 2013; 12(11):847.

Scott M Hammond. An overview of microRNAs. Adv Drug Deliv Rev 2015; 87:3–14.

Nicole Ludwig, Petra Leidinger, Kurt Becker, Christina Backes, Tobias Fehlmann, Christian Pallasch, Steffi Rheinheimer, Benjamin Meder, Cord St¨ahler, Eckart Meese, et al. Distribution of mirna expression across human tissues. Nucleic Acids Res 2016; 44(8):3865–3877.

Tim Kehl, Christina Backes, Fabian Kern, Tobias Fehlmann, Nicole Lud- wig, Eckart Meese, Hans-Peter Lenhof, and Andreas Keller. About MicroRNAs, MicroRNA seeds, target genes and target pathways. Oncotarget 2017; 8(63):107167.

Andrea Ventura and Tyler Jacks. MicroRNAs and cancer: short RNAs go a long way. Cell 2009; 136(4):586–591.

Motoharu Ono, Kayo Yamada, Fabio Avolio, Vackar Afzal, Dalila Ben- Saddek, and Angus I Lamond. Targeted knock-down of mir21 primary transcripts using snomen vectors induces apoptosis in human cancer cell lines. PLoS One 2015; 10(9).

Fanyin Meng, Roger Henson, Hania Wehbe-Janek, Kalpana Ghoshal, Sam- son T Jacob, and Tushar Patel. MicroRNA-21 regulates expression of the pten tumor suppressor gene in human hepatocellular cancer. J Gastroenterol 2007; 133(2):647–658.

Longjiang Xu, Hong Leng, Xin Shi, Jiang Ji, and Jinxiang Fu. Mir-155 promotes cell proliferation and inhibits apoptosis by pten signaling pathway in the psoriasis. Biomed Pharma 2017; 90:524–530.

Masato Yasui, Satomi Matsuoka, and Masahiro Ueda. Pten hopping on the cell membrane is regulated via a positively-charged c2 domain. PLoS Comput Biol 2014; 10(9).

Nguyen HN, Afkari Y, Senoo H, Sesaki H, Devreotes PN, Iijima M. Mechanism of human PTEN localization revealed by heterologous expression in Dictyostelium. Oncogene 2014; 33(50):5688-96.

CB Knobbe, V Lapin, A Suzuki, and TW Mak. The roles of pten in development, physiology and tumorigenesis in mouse models: a tissue-by- tissue survey. Oncogene 2008; 27(41):5398–5415.

Ji-Hyun Chung and Charis Eng. Nuclear-cytoplasmic partitioning of phosphatase and tensin homologue deleted on chromosome 10 (pten) differentially regulates the cell cycle and apoptosis. Cancer Res 2005; 65(18):8096– 8100.

Helga B Salvesen, Ingunn Stefansson, May Britt Kalvenes, Soma Das, and Lars A Akslen. Loss of pten expression is associated with metastatic disease in patients with endometrial carcinoma. Cancer 2002; 94(8):2185–2191.

Jieli Li, Elaine J Tanhehco, and Brenda Russell. Actin dynamics is rapidly regulated by the pten and pip2 signaling pathways leading to myocyte hypertrophy. Am J Physiol-Heart Circ Physiol 2014; 307(11): H1618–H1625.

Ruedi Meili, Atsuo T Sasaki, and Richard A Firtel. Rho rocks pten. Nat cell biol 2005; 7(4):334.

Futoshi Teranishi, Naoko Takahashi, Nan Gao, Yoshimi Akamo, Hiromitsu Takeyama, Tadao Manabe, and Takashi Okamoto. Phosphoinositide 3- kinase inhibitor (wortmannin) inhibits pancreatic cancer cell motility and migration induced by hyaluronan in vitro and peritoneal metastasis in vivo. Cancer Sci 2009; 100(4):770–777.

Charlotte Glinge, Sebastian Clauss, Kim Boddum, Reza Jabbari, Javad Jabbari, Bjarke Risgaard, Philipp Tomsits, Bianca Hildebrand, Stefan K¨a¨ab, Reza Wakili, et al. Stability of circulating blood-based microRNAs– pre-analytic methodological considerations. PloS one 2017; 12(2).

Zhang P, Wu W, Chen Q, Chen M. Non-Coding RNAs and their Integrated Networks. J Integr Bioinform. 2019; 16(3).

Hongxing Zhou and Xuming Zhu. MicroRNA-21 and microRNA-30c as diagnostic biomarkers for prostate cancer: a meta-analysis. Cancer Manag Res 2019; 11:2039.

Ionut Negoi, Sorin Hostiuc, Massimo Sartelli, Ruxandra Irina Negoi, and Mircea Beuran. MicroRNA-21 as a prognostic biomarker in patients with pancreatic cancer–a systematic review and meta-analysis. Am J Surg 2017; 214(3):515–524.

Faraoni I, Antonetti FR, Cardone J, Bonmassar E. miR-155 gene: a typical multifunctional microRNA. Biochim Biophys Acta. 2009; 1792(6):497-505.

Fu, Y., Karstensen, J., and Brandt, P.: On the meridional geostrophic transport in the tropical Atlantic, Ocean Sci. 2017; 13, 531–549.

Kia V, Paryan M, Mortazavi Y, Biglari A, Mohammadi-Yeganeh S. Evaluation of exosomal miR-9 and miR-155 targeting PTEN and DUSP14 in highly metastatic breast cancer and their effect on low metastatic cells. J Cell Biochem 2019; 120(4):5666-5676.

Bordbar M, Darvishzadeh R, Pazhouhandeh M, Kahrizi D. An overview of genome editing methods based on endonucleases. Modern Genetics J 2020; 15(2): 75-92.

Author biographies is not available.