The role of microRNAs in the pathogenesis, diagnosis and treatment of prostate
cancer
M. Khorasani* R. Mahdian** A. Peymani*
*Cellular and Molecular Research Center, Qazvin University of Medical Sciences, Qazvin, Iran **Molecular Medicine Department, Pasteur Institute, Tehran, Iran
Abstract
Prostate cancer is one of the major health problems and the second cause of cancer mortality in men over 40 years age in developed countries. Due to the incomplete screening methods for sensivity and spesificity detection prostate cancer, alternative methods with more specificity than are desired. With recent advances in molecular technology, numerous biomarkers have been suggested for the screening of prostate cancer with greater accuracy. MicroRNAs are oligonucleotides with 18-24 length that have key roles in post-transcriptional regulation of gene expression as well as other cellular process (apoptosis, cell proliferation, differentiation and angiogenesis). Many studies have demonstrated changing of the expression levels of microRNAs in prostate cancer patients. Therefore, they can be implemented for the development of prognostic or diagnostic biomarkers. Owing to microRNAs can target molecular signaling pathways and genes involved in prostate cancer, they may also be applicable for therapeutic purposes. In this review article, we explain the roles of microRNAs in different cancer pathways and specifically the pathogenesis, diagnosis and treatment of prostate cancer.
Keywords: Prostate Cancer, MicroRNAs, Biomarkers
Citation: Khorasani M, Mahdian R, Peymani A. The role of microRNAs in the pathogenesis,
diagnosis and treatment of prostate cancer. J Qazvin Univ Med Sci. 2016; 20 (3): 65-74.
Corresponding Address: Amir Peymani, Qazvin University of Medical Sciences, Cellular and Molecular Research Center, Qazvin, Iran
Email: a.peymani@gmail.com Tel: +98-28-33324971 Received: 9 Jan 2016 Accepted: 3 Apr 2016
66 ﻦﯾوﺰﻗ ﯽﮑﺷﺰﭘ مﻮﻠﻋ هﺎﮕﺸﻧاد ﯽﻤﻠﻋ ﻪﻠﺠﻣ هرﺎﻤﺷ ،ﻢﺘﺴﯿﺑ لﺎﺳ ، 3 ﯽﭘ رد ﯽﭘ) 86 و دادﺮﻣ ،( ﻬﺷ رﻮﯾﺮ 1395 ﻪﻟﺎﻘﻣ / يروﺮﻣ
ﺰﯾر ﺶﻘﻧ
RNA
تﺎﺘﺳوﺮﭘ نﺎﻃﺮﺳ نﺎﻣرد و ﺺﯿﺨﺸﺗ ،ﺶﯾاﺪﯿﭘ رد ﺎﻫ
ﯽﻧﺎﺳاﺮﺧ ﻢﯾﺮﻣ * نﺎﯾﺪﻬﻣ ﺎﺿر ﺮﺘﮐد ** ﯽﻧﺎﻤﯿﭘ ﺮﯿﻣا ﺮﺘﮐد * * ﺰﮐﺮﻣ ﻘﺤﺗ ﯿ تﺎﻘ ﻟﻮﻠﺳ ﯽ و ﻟﻮﮑﻟﻮﻣ ﯽ هﺎﮕﺸﻧاد مﻮﻠﻋ ﮑﺷﺰﭘ ﯽ وﺰﻗ ﯾ ﻦ ناﺮﯾا ،ﻦﯾوﺰﻗ ، ** ﯽﻟﻮﮑﻟﻮﻣ ﯽﮑﺷﺰﭘ ﺶﺨﺑ ناﺮﯾا ،ناﺮﻬﺗ ،ناﺮﯾا رﻮﺘﺳﺎﭘ ﻮﺘﯿﺘﺴﻧا وﺆﺴﻣ هﺪﻨﺴﯾﻮﻧ سردآ :ل وﺰﻗ ﯾ ،ﻦ راﻮﻠﺑ ﻬﺷ ﯿﺪ ،ﺮﻨﻫﺎﺑ ﺰﮐﺮﻣ ﻘﺤﺗ ﯿ تﺎﻘ ﻟﻮﻠﺳ ﯽ و ﻟﻮﮑﻟﻮﻣ ﯽ هﺎﮕﺸﻧاد مﻮﻠﻋ ﮑﺷﺰﭘ ﯽ وﺰﻗ ﯾ ،ﻦ ﻦﻔﻠﺗ 33324971 - 028 Email: a.peymani@gmail.com ﻓﺎﯾرد ﺦﯾرﺎﺗ :ﺖ 19 / 10 / 94 :شﺮﯾﺬﭘ ﺦﯾرﺎﺗ 15 /1 / 95 هﺪﯿﮑﭼ نﺎﻃﺮﺳ تﺎﺘﺳوﺮﭘ ﯾ ﻊﯾﺎﺷ زا ﯽﮑ ﻦﯾﺮﺗ يرﺎﻤﯿﺑ يﺎﻫ هﺪﻨﻨﮐﺪﯾﺪﻬﺗ ﺖﻣﻼﺳ نادﺮﻣ ﻦﯿﻣود و ﻞﻣﺎﻋ گﺮﻣ يﻻﺎﺑ نادﺮﻣ 40 ﻪـﺑ لﺎـﺳ ﺖـﻠﻋ نﺎﻃﺮـﺳ رد يﺎﻫرﻮﺸﮐ ﻪﻌﺳﻮﺗ ﻪﺘﻓﺎﯾ ﺖﺳا . يرادرﻮﺧﺮﺑ مﺪﻋ ﺖﻠﻋ ﻪﺑ نﻮﻣزآ يﺎﻫ لﺎﺑﺮﻏ يﺮﮔ زا ﯽﻓﺎﮐ ﺖﯿﺳﺎﺴﺣ و ﯽﮔﮋﯾو ﯽـﭘ و ﺺﯿﺨﺸﺗ ﺖﻬﺟ نﺎـﻣرد ﺪـﻧور يﺮـﯿﮔ تﺎﺘﺳوﺮﭘ نﺎﻃﺮﺳ شور ، يﺎﺟ يﺎﻫ ﺶﯿﺑ ﺖﯿﺻﺎﺼﺘﺧا ﺎﺑ ﻦﯾﺰﮔ ﺖـﺳا ﻪـﺘﻓﺮﮔ راﺮـﻗ ﻪﺟﻮﺗ درﻮﻣ ﺮﺗ يروﺎـﻨﻓ ﺖﻓﺮـﺸﯿﭘ ﺎـﺑ هزوﺮـﻣا . ﺖـﺴﯾز ،ﯽﻟﻮـﮑﻟﻮﻣ يﺎـﻫ نﺎﺸﻧ دﺪﻌﺘﻣ يﺎﻫﺮﮔ ي لﺎﺑﺮﻏ ﺖﻬﺟ ﻖﯿﻗد يﺮﮔ ﺮﺗ هﺪﺷ ﯽﻓﺮﻌﻣ تﺎﺘﺳوﺮﭘ نﺎﻃﺮﺳ ﺰﯾر .ﺪﻧا RNA لﻮﮑﻟﻮﻣ ،ﺎﻫ يﺎﻫ RNA لﻮـﻃ ﺎـﺑ 18 ﺎـﺗ 24 ﻠﮐﻮﻧ ﺌ ﺪـﯿﺗﻮ ﻪﮐ ﺪﻨﺘﺴﻫ ﯽﻟﻮﻠﺳ گﺮﻣ) ﯽﻟﻮﻠﺳ يﺎﻫﺪﻨﯾاﺮﻓ و ﯽﺴﯾﻮﻧور زا ﺲﭘ نژ نﺎﯿﺑ ﻢﯿﻈﻨﺗ رد گر و ﺰﯾﺎﻤﺗ ،ﯽﻟﻮﻠﺳ ﺮﯿﺜﮑﺗ ، ﯽﯾاز .ﺪﻧراد يﺪﯿﻠﮐ ﺶﻘﻧ ( ناﺰـﯿﻣ تاﺮﯿﯿﻐﺗ نﺎﯿﺑ ﺰﯾر RNA ﻪﻧﻮﻤﻧ رد دﻮﺟﻮﻣ يﺎﻫ ﺎﻫ ي نارﺎﻤﯿﺑ ﻒﻠﺘﺨﻣ تﺎﺘﺳوﺮﭘ نﺎﻃﺮﺳ ﻪﺑ ﻼﺘﺒﻣ ﻌﻟﺎﻄﻣ رد ﻪ يﺎﻫ شراﺰﮔ ،ﻒﻠﺘﺨﻣ هﺪﺷ ﺪﻧا ﯽﻣ ﻪﮐ ﺪﻨﻧاﻮﺗ ﻪـﺑ ناﻮـﻨﻋ نﺎﺸﻧ ﺖﺴﯾز ﭘ و ﺺﯿﺨﺸﺗ رد شزرا ياراد ﺮﮔ ﯿ ﺶ ﯽﻬﮔآ ﺪﻧﻮﺷ هدﺎﻔﺘﺳا نآ زا . ﺰﯾر ﻪﮐ ﺎﺟ RNA مﺎﯿﭘ يﺎﻫﺮﯿﺴﻣ ﺎﻫ نژ و دﺪﻌﺘﻣ ﯽﻟﻮﮑﻟﻮﻣ نﺎﺳر ﻞـﯿﺧد يﺎﻫ يرﺎﻤﯿﺑ رد ﯽﻣ راﺮﻗ فﺪﻫ ار تﺎﺘﺳوﺮﭘ نﺎﻃﺮﺳ ﯽﯾاز ﯽﻣ ،ﺪﻨﻫد نآ زا ناﻮﺗ ﺎﻫ ﯽﻧﺎﻣرد فاﺪﻫا ياﺮﺑ دﺮﮐ هدﺎﻔﺘﺳا يروﺮﻣ ﻪﻌﻟﺎﻄﻣ ﻦﯾا رد . ، ﺰﯾر ﺶﻘﻧ RNA ﺎﻫ دﺎﺠﯾا رد ﻪﺑ و نﺎﻃﺮﺳ ﯽﺻﺎﺼﺘﺧا رﻮﻃ يرﺎﻤﯿﺑ نﺎﻣرد و ﺺﯿﺨﺸﺗ ،ﯽﯾاز ﯽﺳرﺮﺑ تﺎﺘﺳوﺮﭘ نﺎﻃﺮﺳ هﺪﺷ .ﺖﺳا هژاوﺪﯿﻠﮐ :ﺎﻫ ﺰﯾر ،تﺎﺘﺳوﺮﭘ نﺎﻃﺮﺳ RNA ﺎﻫ ، نﺎﺸﻧ ﺖﺴﯾز ﺎﻫﺮﮔ
:ﻪﻣﺪﻘﻣ
ﻊﯾﺎــﺷ زا ﯽــﮑﯾ ناﻮــﻨﻋ ﻪــﺑ تﺎﺘــﺳوﺮﭘ نﺎﻃﺮــﺳ
ﻦﯾﺮــﺗ
يرﺎﻤﯿﺑ
د و نﺎﻬﺟ رد نادﺮﻣ ﺖﻣﻼﺳ هﺪﻨﻨﮐﺪﯾﺪﻬﺗ يﺎﻫ
و
ﻦﯿﻣ
ﻮـﺸﮐ رد نﺎﻃﺮﺳ ﺖﻠﻋ ﻪﺑ نادﺮﻣ گﺮﻣ ﻞﻣﺎﻋ
ﻪﻌـﺳﻮﺗ يﺎﻫر
ﻪﺑ ﻪﺘﻓﺎﯾ
ﯽﻣ رﺎﻤﺷ
.دور
)1 (ﻌﻟﺎﻄﻣ
ﻪ
ﺎﻫ
هداد نﺎـﺸﻧ
ﺪـﻧا
لﺎـﺳ رد
2014
،ﺎـﮑﯾﺮﻣا هﺪﺤﺘﻣ ﺖﻟﺎﯾا رد يدﻼﯿﻣ
233
راﺰـﻫ
درﻮـﻣ
ﯾﺪﺟ
شراﺰـﮔ تﺎﺘﺳوﺮﭘ نﺎﻃﺮﺳ ﺪ
و
زا
ناﺰـﯿﻣ ﻦـﯾا
29480
ﺖـﺳا هﺪـﺷ ﯽﻬﺘﻨﻣ گﺮﻣ ﻪﺑ درﻮﻣ
.
)2 (ﻪـﭼﺮﮔا
رﺎـﻣآ ﻦـﯾا
رد
ﻦﯿﯾﺎﭘ رﺎﯿﺴﺑ ناﺮﯾا ﻪﻠﻤﺟ زا ﯽﯾﺎﯿﺳآ يﺎﻫرﻮﺸﮐ
ﺮﺗ
،هدﻮﺑ
ﯽـﻟو
لﺎﺳ ﯽﻃ
ﺮﯿﺧا يﺎﻫ
داﺪﻌﺗ
شراﺰﮔ
يﺎﻫ
ﺶﯾاﺰـﻓا ﻼﺘﺒﻣ داﺮﻓا
ﻪﺘﻓﺎﯾ
.ﺖﺳا
ﻪـﺑ ناﺮـﯾا رد تﺎﺘﺳوﺮﭘ نﺎﻃﺮﺳ ﺮﺿﺎﺣ لﺎﺣ رد
ناﻮﻨﻋ
ﻦﯿﻤﺘﻔﻫ
ﻪﺑ نادﺮﻣ ﺮﯿﻣ و گﺮﻣ ﻞﻣﺎﻋ
نﺎﻃﺮـﺳ ﺖﻠﻋ
ﻪﺑ
ﯽﻣ رﺎﻤﺷ
دور
.
)3 و4 (ﯽﻠﺻا
رد تﺎﺘﺳوﺮﭘ نﺎﻃﺮﺳ ﺎﺑ ﻂﺒﺗﺮﻣ ﺮﻄﺧ ﻞﻣاﻮﻋ ﻦﯾﺮﺗ
ﻌﻟﺎﻄﻣ
ﻪ
يﺎﻫ
ﻒﻠﺘﺨﻣ
،
داﮋﻧ ،ﻻﺎﺑ ﻦﺳ
و
ﯽﻠﯿﻣﺎـﻓ ﻪﻘﺑﺎـﺳ
ﺮـﮐذ
هﺪﺷ
.ﺪﻧا
)5 و6 (ﻪﺘـﺴﻫآ ﺪـﺷر ﺎﺑ يرﺎﻤﯿﺑ ﮏﯾ تﺎﺘﺳوﺮﭘ نﺎﻃﺮﺳ
و ﺖﺳا
رد
نارﺎﻤﯿﺑ زا يرﺎﯿﺴﺑ
،
هﺪﻨﻫدراﺪـﺸﻫ يﺪـﺟ ﻢﯾﻼﻋ
.دراﺪﻧ دﻮﺟو
ﻪـﻌﺟاﺮﻣ ﮏـﺷﺰﭘ ﻪـﺑ رﺎﻤﯿﺑ دﺮﻓ ﯽﻧﺎﻣز ﻦﯾاﺮﺑﺎﻨﺑ
ﯽﻣ
ﻪﮐ ﺪﻨﮐ
ﻪﺑ
ﺎﺑ هاﺮﻤﻫ ﺎﯾ ﻪﺘﻓﺮﺸﯿﭘ ﻪﻠﺣﺮﻣ
ﺖﺳد
ﻪـﺑ يزاﺪـﻧا
نﺪﺑ ﺮﮕﯾد طﺎﻘﻧ
ا هﺪﺷ دراو
ﺖﺳ
.
ﻦﯾا زا
يرﺎﻤﯿﺑ ﯽﯾﺎﺳﺎﻨﺷ ور
رد
ﯽﯾاﺪـﺘﺑا ﻞﺣاﺮﻣ
،
رد
ﺶﯾﺎـﭘ
نﺎـﻣرد و
ﯽـﻤﻬﻣ ﺶـﻘﻧ نآ
.دراد
)5 (ﺮﺿﺎﺣ لﺎﺣ رد
نﻮﻣزآ
لﺎﺑﺮﻏ ﺖﻬﺟ دراﺪﻧﺎﺘﺳا
ﻪﯿﻟوا يﺮﮔ
ﻞﻣﺎﺷ تﺎﺘﺳوﺮﭘ نﺎﻃﺮﺳ
نﻮﻣزآ
هزاﺪﻧا
ﯽﻣﺮـﺳ ﺢﻄـﺳ يﺮﯿﮔ
ﯽﺘﻧآ
ـﻨﯾﺎﻌﻣ و تﺎﺘـﺳوﺮﭘ ﯽﺻﺎﺼﺘﺧا نژ
ﻪ
يﺪـﻌﻘﻣ ﯽﺘـﺸﮕﻧا
ﺖﺳا
.
)7 (لﺎﺣ ﻦﯾا ﺎﺑ
ﺺﯿﺨـﺸﺗ ﺖﯿـﺳﺎﺴﺣ
يرﺎـﻤﯿﺑ
ﯽـﻌﻄﻗ
ﻧ
ﺖﺴﯿ
ﻫﺎﮔ و
ﯽ
ﻼﺘﺒﻣ داﺮﻓا
،
ﯽﺘﻧآ
تﺎﺘـﺳوﺮﭘ ﯽـﺻﺎﺼﺘﺧا نژ
ﺪﻧراد ﯽﻌﯿﺒﻃ
.
زاﺪـﻧا ﺶﯾﺎـﻣزآ
ه
ﯽـﺘﻧآ يﺮـﯿﮔ
ﯽـﺻﺎﺼﺘﺧا نژ
ﯽﻣ تﺎﺘﺳوﺮﭘ
و تﺎﺘـﺳوﺮﭘ بﺎـﻬﺘﻟا نﻮـﭼ يدراﻮـﻣ رد ﺪﻧاﻮﺗ
ﯽﮔرﺰﺑ
شﻮﺧ
تﺎﺘـﺳوﺮﭘ ﻢﯿﺧ
ﺶﯾاﺰـﻓا ﺰـﯿﻧ
ﺪـﺑﺎﯾ
.
ﻦـﯾا زا
ور
ﻪـﻧﻮﻤﻧ ،يرﺎـﻤﯿﺑ ﯽﻌﻄﻗ ﺺﯿﺨﺸﺗ ﺖﻬﺟ
و ﺖـﻓﺎﺑ زا يرادﺮـﺑ
ﯽﺳرﺮﺑ مﺎﺠﻧا
ﺐﯿﺳآ
ﯽﺳﺎﻨﺷ
وﺮﺿ
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ﺖﺳا
.
)8 (ا
نآ ز
ﻪـﮐ ﺎـﺟ
ﻪـﮐ يرﺎﯿـﺴﺑ داﺮـﻓا ﻪﻧﻻﺎﺳ
ﻼﺘـﺒﻣ
تﺎﺘـﺳوﺮﭘ نﺎﻃﺮـﺳ ﻪـﺑ
ﯿﻧ
ﺪﻨﺘﺴ
،
ﻪـﻧﻮﻤﻧ زا ﯽﺷﺎﻧ درد
ار يرادﺮـﺑ
ﻞـﻤﺤﺗ
ﯽـﻣ
ﺪـﻨﻨﮐ
،
زا هدﺎﻔﺘﺳا
نﺎﺸﻧ ﺖﺴﯾز
ﺮﮔ
ﻦﯾا رﺎﻨﮐ رد ﺎﻫ
نﻮﻣزآ
ﯽﻣ ﺎﻫ
ﺪﻧاﻮﺗ
ا رد
ﯽﮔﮋﯾو ﺶﯾاﺰﻓ
ﺶﯾﺎﻣزآ نﺎﻨﯿﻤﻃا و
يﺎﻫ
ﯽﺼﯿﺨﺸﺗ
ﺆﻣ
ﺮﺛ
ﺪﺷﺎﺑ
.
)9 -7(تﺎﺘﺳوﺮﭘ نﺎﻃﺮﺳ ﻪﺑ ﻼﺘﺒﻣ داﺮﻓا
،
ﻪﯿﻟوا ﻞﺣاﺮﻣ رد
ﺖﺒﺴﻧ
ﺎﺑ نﺎﻣرد ﻪﺑ
نﻮﻣرﻮﻫ
ﺦـﺳﺎﭘ
ﯽـﻣ
ﯽـﻟو ،ﺪـﻧﺮﯿﮔ
ﺖـﺷﺬﮔ ﺎـﺑ
دراو و موﺎﻘﻣ نﺎﻣرد ﻪﺑ ﺖﺒﺴﻧ يرﺎﻤﯿﺑ
ﻪﻠﺣﺮﻣ
ﺖﺳد
يزاﺪـﻧا
ﻪﺑ
ﺮﯾﺎﺳ
نﺪﺑ طﺎﻘﻧ
ﯽﻣ
ﺪﻧﻮﺷ
. ﺑ
ﯽﻣ ﺮﻈﻧ ﻪ
ﺪﺳر
ﺪﻧور ﻪﻌﻟﺎﻄﻣ ﺎﺑ
ﯽـﻣ تﺎﺘـﺳوﺮﭘ نﺎﻃﺮﺳ دﺎﺠﯾا ﺮﯿﺴﻣ رد ﯽﻟﻮﮑﻟﻮﻣ
ﻪـﺑ ناﻮـﺗ
.دﺮﮐ ﮏﻤﮐ يرﺎﻤﯿﺑ ﻦﯾا نﺎﻣرد
) 10 (ﺰﯾر
RNAا ﺎـﻫ
ز
هداﻮﻧﺎـﺧ
RNAيﺎــﻫ
ُﮐﺮﯿﻏ ﮏــﭼﻮﮐ
هزاﺪــﻧا ﺎــﺑ هﺪــﻨﻨﮐﺪ
18
ﺎــﺗ
24
هﺪﺷ ﺖﻈﻓﺎﺤﻣ رﺎﯿﺴﺑ ﻞﻣﺎﮑﺗ ﯽﻃ ﻪﮐﺪﻨﺘﺴﻫ يﺪﯿﺗﻮﺌﻠﮐﻮﻧ
ﺪـﻧا
ﻢﯿﻈﻨﺗ رد و
ﯽـﺴﯾﻮﻧور زا ﺲﭘ
نژ نﺎـﯿﺑ
ﺎـﻫ
يﺪـﯿﻠﮐ ﺶـﻘﻧ
.ﺪــﻧراد
) 10 (ــﻟﺎﻘﻣ ﻦــﯾا رد
ﺰــﯾر ﺶــﻘﻧ ﻪ
RNA،دﺎــﺠﯾا رد ﺎــﻫ
تﺎﺘﺳوﺮﭘ نﺎﻃﺮﺳ نﺎﻣرد و ﺺﯿﺨﺸﺗ
ﺪﺷ ﯽﺳرﺮﺑ
.
شور و داﻮﻣ
ﺎﻫ
:
ﯽﺳرﺮﺑ ﺎﺑ يروﺮﻣ ﻪﻌﻟﺎﻄﻣ ﻦﯾا
و ﻞﻬﭼ
ﺮﺒﺘﻌﻣ ﻪﻟﺎﻘﻣ ﺶﺷ
) ﻞﻣﺎﮐ ﻦﺘﻣ ياراد ﯽﻤﻠﻋ
2010
ﺎﺗ
2015
نﺎﻃﺮﺳ درﻮﻣ رد (
ﺰﯾر ﺶﻘﻧ و تﺎﺘﺳوﺮﭘ
RNAيرﺎﻤﯿﺑ ﺮﯿﺴﻣ رد ﺎﻫ
مﺎـﺠﻧا ﯽﯾاز
ﮏﻧﺎﺑ زا ﻦﯿﻨﭽﻤﻫ .ﺪﺷ
ﯽﻟﻮـﮑﻟﻮﻣ و ﯽـﮑﯿﺘﻧژ ﯽﺗﺎﻋﻼﻃا يﺎﻫ
ﺪــﻨﻧﺎﻣ ﻒــﻠﺘﺨﻣ
KEEG Pathway Databases
ﺎـــﯾ
DIANA mirPathيﺎﻫﺮﯿﺴﻣ نﺎﯿﻣ طﺎﺒﺗرا ﯽﺳرﺮﺑ ﺖﻬﺟ
ﺶـﻘﻧ ﻦﯿـﻨﭽﻤﻫ و تﺎﺘـﺳوﺮﭘ نﺎﻃﺮـﺳ رد ﻞﯿﺧد ﯽﻟﻮﮑﻟﻮﻣ
ﺰﯾر
RNAيرﺎﻤﯿﺑ رد ﺎﻫ
تﺎﺘـﺳوﺮﭘ نﺎﻃﺮﺳ ﺖﻓﺮﺸﯿﭘ و ﯽﯾاز
.ﺪﺷ هدﺎﻔﺘﺳا
ﺖﺴﯾز
ﺰﯾر ﯽﯾاز
RNAنﺎﻃﺮﺳ و ﺎﻫ
:
ﺖﺴﯾز
ياز
ﺰﯾر
RNAﺎﻫ
رد اﺪـﺘﺑا و ﻪـﻠﺣﺮﻣ ﻦﯾﺪﻨﭼ ﯽﻃ
ﯽـﻣ مﺎـﺠﻧا ﻢـﺳﻼﭘﻮﺘﯿﺳ رد ﺲﭙﺳ و ﻪﺘﺴﻫ
.دﻮـﺷ
نژ
يﺎـﻫ
ﺰـﯾر
RNAﺎـﻫ
ﻂـﺳﻮﺗ
آ
ﻢﯾﺰـﻧ
RNAﯽـﻠﭘ
زاﺮـﻣ
II/IIIﻪـﺑ
ﻦﯾزﺎﻏآ ﺖﺷﻮﻧور
Pri-microRNAﯽﻣ ﯽﺴﯾﻮﻧور
ﻪـﮐ دﻮﺷ
ﻪﻗﺎﺳ رﺎﺘﺧﺎﺳ
ﻪﻘﻠﺣ
دراد
يﺎﻬﺘﻧا رد و
5'
ﯽﻟاﻮﺗ دﻮﺧ
ﮏﻫﻼﮐ
و
يﺎﻬﺘﻧا
3'
ﯽﻠﭘ
ﻪـﻠﯿﻧدآ
دراد
.
Pri-microRNAﺮﯿـﺴﻣ رد
ﻪﺑ نﺪﺷ ﻞﯾﺪﺒﺗ
ﺰﯾر
RNAرد ﻎﻟﺎﺑ
ﺪﻨﯾاﺮﻓ
ﺖﺴﯾز
ﯽﯾاز
رﺎﺑ ود
ﯽﻣ شﺮﺑ
يﺎـﻫ ﻢﯾﺰـﻧآ ﻂـﺳﻮﺗ ﺮـﻣا ﻦـﯾا .دﻮﺷ
RNaseIIIو ﻪﺘﺴﻫ رد ﺮﻘﺘﺴﻣ
ﻞﻣﺎـﺷ ﺐـﯿﺗﺮﺗ ﻪـﺑ ﻢـﺳﻼﭘﻮﺘﯿﺳ
ﺎـﺷورد
) Drosha (و
ﺮﺴﯾاد
) Dicer (ﯽـﻣ مﺎـﺠﻧا
.دﻮـﺷ
ﺖـﺷﻮﻧور
شﺮﺑ زا ﻞﺻﺎﺣ
ﺎﺷورد
،
Pre-microRNAﻣﺎﻧ
ﯽﻣ هﺪﯿ
دﻮـﺷ
و
ﯽﻟاﻮــﺗ
دوﺪــﺣ
70
ﻠﮐﻮﻧ
ﺌ
ﺪــﯿﺗﻮ
دراد ي
.
Pre-microRNAﺳﻮﺗ
ﻞﻗﺎﻧ ﻂ
ﻦﯿﺗرﻮﭙﺴﮐا
-5
و
ﻞـﻣﺎﻋ
ﯽـﮑﻤﮐ
Ran-GTPزا
ﯽﻣ ﻞﻘﺘﻨﻣ ﻢﺳﻼﭘﻮﺘﯿﺳ ﻪﺑ ﻪﺘﺴﻫ
ﻂـﺳﻮﺗ شﺮـﺑ ﻦﯾﺮﺧآ .دﻮﺷ
ﺮﺴﯾاد ﻪﻋﻮﻤﺠﻣ
ﻞـﺼﺘﻣ ﻦﯿﺌﺗوﺮـﭘ و
ﻪـﺑ هﺪﻧﻮـﺷ
RNAود
ﻪﺘــﺷر
يا
) TRBP2 (ﯽــﻣ مﺎــﺠﻧا
دﻮــﺷ
.
) 11 (زا ﻪﺘــﺷر ﮏــﯾ
ﺰﯾر
RNAدوﺪـﺣ ﻪﮐ
18
ﺎـﺗ
24
ﺎـﺑ دراد لﻮـﻃ ﺪـﯿﺗﻮﺌﻠﮐﻮﻧ
ﯽــﮑﻤﮐ ﻦﯿﺌﺗوﺮــﭘ
تﺎــﻧﻮﮔرآ
2،
ﻪــﻋﻮﻤﺠﻣ
شﻮﻣﺎــﺧ
هﺪــﻨﻨﮐ
) RNA-induced silencing complex: RISC (
ار
ﻞﯿﮑﺸﺗ
ﯽﻣ
.ﺪﻫد
ﺰﯾر
RNAﯽﻣ
ﺪﻧاﻮﺗ
ﯽﻟاﻮﺗ ﻪﺑ
'
3
ﻞـﻤﮑﻣ
زا
mRNAﯿﻐﺗ و دﻮﺷ ﻞﺼﺘﻣ فﺪﻫ
ﯿ
تاﺮ
ار ﯽﺴﯾﻮﻧور زا ﺲﭘ
ﻢﯿﻈﻨﺗ
.ﺪﻨﮐ
ﻞﻣﺎﮐ
ندﻮﺑ
ﯽﻟاﻮﺗ
ﺰﯾر
RNAو
mRNAفﺪﻫ
نآ
،
ﺐﺒﺳ
ﻪﻌﻄﻗ
ﻪﻌﻄﻗ
نﺪﺷ
mRNAو
ﯽﯾﺰﺟ
ندﻮﺑ
ﻦﯾا
لﺎﺼﺗا
،
ﻪﻤﺟﺮﺗ رﺎﻬﻣ ﺐﺒﺳ
mRNAﯽﻣ فﺪﻫ
دﻮﺷ
.
) 12 (ﺶﻘﻧ
ﺰﯾر
RNAﺎﻫ
نﺎﻃﺮﺳ ﺶﯾاﺪﯿﭘ رد
:
ﻖﯿﻘﺤﺗ
ﺎـﻫ
هداد نﺎـﺸﻧ
نژ زا ﯽـﻤﯿﻧ زا ﺶﯿـﺑ ﺪـﻧا
يﺎـﻫ
ُﮐ
ﺰﯾر هﺪﻨﻨﮐﺪ
RNAنﺎﻃﺮـﺳ ﺎـﺑ ﻂﺒﺗﺮﻣ ﯽﻣﻮﻧژ ﯽﺣاﻮﻧ رد ﺎﻫ
هﺪﻨﻨﮑﺷ ﯽﺣاﻮﻧ رد ﺎﯾ
ﻪﺘﻓﺮﮔ راﺮﻗ مﻮﻧژ
ﺪﻧا
.
ﻣ ناﻮـﻨﻋ ﻪﺑ
ـﺜ
لﺎ
،
miR-34aموزﻮﻣوﺮﮐ هﺪﻨﻨﮑﺷ هﺎﮕﯾﺎﺟ رد
11q23-24راﺮﻗ
ﻪﮐ دراد
نژ ﻦـﯾا
ﻪﻨﯿـﺳ نﺎﻃﺮـﺳ ﻪـﺑ ﻼﺘـﺒﻣ نارﺎـﻤﯿﺑ رد
و
نﺎﻃﺮﺳ
ﻪﯾر
ﯽـﻣ فﺬﺣ
دﻮـﺷ
.
) 13 (ﺰـﯾر
RNAﻂﯾاﺮـﺷ رد ﺎـﻫ
رد نﺪــﺑ ﯽــﻌﯿﺒﻃ ﯽﮑﯾژﻮــﻟﻮﯾﺰﯿﻓ
ﺪــﻨﯾاﺮﻓ
ﺎﻫ
ﯾ
ﯽ
ﺪــﻨﻧﺎﻣ
ﺮــﯿﺜﮑﺗ
و ﻞﻣﺎﮑﺗ ،ﯽﻟﻮﻠﺳ
ﯽﻟﻮﻠـﺳ گﺮﻣ
.ﺪـﻧراد ﯽـﻤﯿﻈﻨﺗ ﺶـﻘﻧ
) 14 (نﺎﯿﺑ تاﺮﯿﯿﻐﺗ ﯽﺳرﺮﺑ زا ﻞﺻﺎﺣ ﺞﯾﺎﺘﻧ
ﻪﯾﺎﻤﻧ
ﺰﯾر
RNAرد ﺎﻫ
لﻮﻠﺳ و ﺖﻓﺎﺑ
يﺎﻫ
ﯽﻧﺎﻃﺮﺳ
يﺎﺠﺑﺎﻧ نﺎﯿﺑ ﻪﺑ
ﺰـﯾر
RNAﺎـﻫ
ﺰﯾر .دراد ﺖﻟﻻد
RNAرد ﻞـﯿﺧد دﺪـﻌﺘﻣ يﺎﻫﺮﯿـﺴﻣ رد ﺎﻫ
ﺶﯾاﺪﯿﭘ
ﻪـﻠﻤﺟ زا ،نﺎﻃﺮـﺳ يوﺮـﺸﯿﭘ و
گر
ﯽـﯾاز
،
ﺪـﻨﯾاﺮﻓ
ﯿﭘا لﺎﻘﺘﻧا
لﺎﯿﻠﺘ
-
ﯿﺸﻧاﺰﻣ
ﯽﻤ
و
ﺖﺳد
يزاﺪﻧا
ﻪـﮐ ﺪـﻧراد ﺶﻘﻧ
نﺎﯿﺑ ﺖﻠﻋ ﻪﺑ
ﺐﻠﻏا
ﺰﯾر
RNAنآ زا هدﺎﻔﺘﺳا ،ﺎﻫ
ناﻮﻨﻋ ﻪﺑ ﺎﻫ
68 ﻦﯾوﺰﻗ ﯽﮑﺷﺰﭘ مﻮﻠﻋ هﺎﮕﺸﻧاد ﯽﻤﻠﻋ ﻪﻠﺠﻣ هرﺎﻤﺷ ،ﻢﺘﺴﯿﺑ لﺎﺳ ، 3 ﯽﭘ رد ﯽﭘ) 86 و دادﺮﻣ ،( ﻬﺷ رﻮﯾﺮ 1395 ﻪﻟﺎﻘﻣ / يروﺮﻣ
نﺎﺸﻧ ﺖﺴﯾز
ﺮﮔ
ﯽـﺼﯿﺨﺸﺗ
ياﺮـﺑ
ﺑ ﺺﯿﺨـﺸﺗ
ﻬ
رد و مﺎـﮕﻨ
ﻊﻗاﻮﻣ ﯽﺧﺮﺑ
ياﺮﺑ
ﻦﯿﯿﻌﺗ
ﺶﯿﭘ
ﯽﻬﮔآ
ﮏـﻤﮐ يرﺎﻤﯿﺑ
هﺪـﻨﻨﮐ
ﺖﺳا
هرﺎﻤﺷ لوﺪﺟ)
1
.(
) 22 -15 (ﺰﯾر
RNAمﺎﯿﭘ ﺮﯿﺴﻣ و ﺎﻫ
:نژورﺪﻧآ هﺪﻧﺮﯿﮔ ﯽﻧﺎﺳر
ﻣ ﯽﻟﻮﮑﻟﻮﻣ يﺎﻫﺮﯿﺴﻣ زا ﯽﮑﯾ
ﺛﺆ
دﺮﺒـﺸﯿﭘ و دﺎـﺠﯾا رد ﺮ
تﺎﺘﺳوﺮﭘ نﺎﻃﺮﺳ
ﺮﯿـﺴﻣ
مﺎـﯿﭘ
ﯽﻧﺎـﺳر
ﻪـﺑ ﻪﺘـﺴﺑاو
هﺪـﻧﺮﯿﮔ
نژورﺪﻧآ
ﺖﺳا
هرﺎﻤﺷ ﻞﮑﺷ)
1(
.
) 23 (ﺶـﻘﻧ
ﺰـﯾر
RNAﺎـﻫ
و
مﺎﯿﭘ
نژورﺪﻧآ هﺪﻧﺮﯿﮔ زا ﯽﺷﺎﻧ
ود
ﻪﯾﻮﺳ
ﺖﺳا
؛
ﻪﮐ يﻮﺤﻧ ﻪﺑ
زا ﯽـﺧﺮﺑ
ﺰـﯾر
RNAﺎــﻫ
ﻂـﺳﻮﺗ
هﺪــﻧﺮﯿﮔ
ﻢﯿــﻈﻨﺗ نژورﺪـﻧآ
ﯽﻣ
ﻮﺷ
ﻧﺪ
و
لﻮﮑﻟﻮﻣ يور ﺮﺑ ﺮﮕﯾد ﯽﺧﺮﺑ
ﻦﯾا رد دﻮﺟﻮﻣ يﺎﻫ
ﺮﯿﺴﻣ
ﺗ ﺶﻘﻧ
ﺛﺄ
ﻢﯿﻈﻨﺗ و راﺬﮔﺮﯿ
هﺪﻨﻨﮐ
دﺮﮑﻠﻤﻋ ﺮﺑ ﺖﯾﺎﻬﻧ رد و
زا ﯽــﺷﺎﻧ
ــﯿﭘ
مﺎ
هﺪــﻧﺮﯿﮔ ﯽﻧﺎــﺳر
نژورﺪــﻧآ
ﯽــﻤﯿﻈﻨﺗ ﺶــﻘﻧ
.ﺪﻧراد
) 23 (لﺎﺳ رد
زا هدﺎﻔﺘﺳا ﺎﺑ ﺮﯿﺧا يﺎﻫ
،يراوﺮﮑﯿﻣ يروﺎﻨﻓ
ﻊﻣﺎــﺟ نﺎــﯿﺑ
ﺰــﯾر
RNAﺎــﻫ
رد
هدر
نﺎﻃﺮــﺳ ﯽﻟﻮﻠــﺳ يﺎــﻫ
تﺎﺘﺳوﺮﭘ
ترﻮﺻ ﻪﺑ
نژورﺪـﻧآ زا ﻞﻘﺘﺴﻣ و ﻪﺘﺴﺑاو
ﯽـﺳرﺮﺑ
.ﺖﺳا هﺪﺷ
ﻦﯾا رد
ﻪﻌﻟﺎﻄﻣ
،ﺎﻫ
رد
هدر
ﯽﻟﻮﻠﺳ يﺎﻫ
هﺪﺷ رﺎﻤﯿﺗ
نژورﺪﻧآ ﺎﺑ
ﯽﻋﻮﻨـﺼﻣ
R1881،
ﻪـﺑ ﻪﺘـﺴﺑاو نﺎـﯿﺑ ﺶﯾﺰـﻓا
نژورﺪﻧآ
رد
ﺰﯾر
RNA:ﺖﺳا هﺪﺷ شراﺰﮔ ﺮﯾز يﺎﻫ
miR-594 ، miR-16 ، 21 29b ، miR-148a ، miR-29c ، miR-106a ، miR-17-5p ، miR-20a ، miR-20b ، miR-29a ، miR-19b ، miR-93 ، Let-7g ، Let-7dو
miR-125.
) 24 ( لوﺪﺟ 1 - ﺰﯾر RNA دﺎﺠﯾا ﺪﻨﯾاﺮﻓ رد ﻞﯿﺧد يﺎﻫ نﺎﻃﺮﺳ ﻞﮑﺷ 1 - ﺶﻘﻧ ﺰﯾر RNA رد ﺎﻫ ﺮﯿﺴﻣ مﺎﯿﭘ ﯽﻧﺎﺳر ﻪﺑ ﻪﺘﺴﺑاو هﺪﻧﺮﯿﮔ نژورﺪﻧآ ﻊﺟﺮﻣ نﺎﻃﺮﺳ دﺎﺠﯾا ﺪﻨﯾاﺮﻓ رد ﺶﻘﻧ فﺪﻫ نژ نﺎﻃﺮﺳ عﻮﻧ RNAﺰﯾر 15 ﯽﯾازگر رﺎﻬﻣ VEGF-A and FGF2 ﺪﺒﮐ يﺎﻫ(رﻻﻮﻠﺳﻮﺗﺎﭙﻫ )لﻮﻠﺳ نﺎﻃﺮﺳ miR-50316 ﯽﯾازگر رﺎﻬﻣ HIF-1a, VEGF,HER2,andHER3 ناﺪﻤﺨﺗ نﺎﻃﺮﺳ miR-125b
17 EMT/METﺪﻨﯾاﺮﻓ ZEB
نﺎﺘﺴﭘ نﺎﻃﺮﺳ ﻪﻧﺎﺜﻣ نﺎﻃﺮﺳ ناﺪﻤﺨﺗ نﺎﻃﺮﺳ
miR-200 family (miR-200a/200b/200c/141/429)
18 EMTﺪﻨﯾاﺮﻓ Snail, ZNF281, IL-6R لﺎﺘﮐرﻮﻟﻮﮐ نﺎﻃﺮﺳ miR-34a
19 EMTﺪﻨﯾاﺮﻓ Notch and IGF1R هﺪﻌﻣ نﺎﻃﺮﺳ MiR-503
20 ﯽﻧﻮﻠﮐ ﻞﯿﮑﺸﺗ و ﻢﺟﺎﻬﺗ ،تﺮﺟﺎﻬﻣ SOX4, TNC نﺎﺘﺴﭘ نﺎﻃﺮﺳ miR-335
21 تﺮﺟﺎﻬﻣ Notch3, CDK4, Cyclin D ﺎﻣﻮﻧﻮﻠﻣ نﺎﻃﺮﺳ miR-206
ﺰﯾر
RNAمﺎﯿﭘ ﺮﯿﺴﻣ و ﺎﻫ
ﯽﻧﺎﺳر
PTEN/Akt:
يﺎﻫﺮﯿﺴﻣ زا ﺮﮕﯾد ﯽﮑﯾ
ﻢﻬﻣ
تﺎﺘﺳوﺮﭘ نﺎﻃﺮﺳ رد
ﻪـﺑ
عﻮــﻧ صﻮــﺼﺧ
،نآ ﯽﻧﻮــﻣرﻮﻫ نﺎــﻣرد ﻪــﺑ موﺎــﻘﻣ
ﺮﯿــﺴﻣ
ﺪﯿﺘﯾزﻮﻨﯾاﻮﻔـــﺴﻓ
3
-ﺎـــﻨﯿﮐ
ز
(PI3K).ﺖـــﺳا
) 25 ( PTENﻦﯿـﻟوا ناﻮـﻨﻋ ﻪـﺑ ﻪﮐ ﺖﺳا يزﺎﺗﺎﻔﺴﻓ دﺮﮑﻠﻤﻋ ﺎﺑ ﯽﻨﯿﺌﺗوﺮﭘ
ﻢﯿﻈﻨﺗ
ﯽـﻓﺮﻌﻣ رﻮـﻣﻮﺗ هﺪـﻨﻨﮐرﺎﻬﻣ و ﺮﯿﺴﻣ ﻦﯾا ﯽﻔﻨﻣ هﺪﻨﻨﮐ
ﻦﯿﺌﺗوﺮﭘ ﯽﭙﮐ داﺪﻌﺗ ﺶﻫﺎﮐ ﻪﺑ ﻪﮐ ﺮﯿﯿﻐﺗ ﻪﻧﻮﮔﺮﻫ .ﺖﺳا هﺪﺷ
PTENﯽﻣ دﻮﺷ ﺮﺠﻨﻣ
ﺪﻧاﻮﺗ
ﺮﯿﺴﻣ دﺮﮑﻠﻤﻋ
ﺪﯿﺘﯾزﻮﻨﯾاﻮﻔـﺴﻓ
3
-ﺎﻨﯿﮐ
ز
و ﺮـﯿﺜﮑﺗ ،ﯽﻟﻮﻠـﺳ ﻪﺧﺮﭼ ﺖﯾﺎﻬﻧ رد و
گر
ار ﯽـﯾاز
ﻫﺎﮐ ﺎﺑ و ﺪﻫد ﺶﯾاﺰﻓا
لﻮﻠـﺳ يﺎـﻘﺑ ﺚﻋﺎﺑ ﯽﻟﻮﻠﺳ گﺮﻣ ﺶ
.دﻮﺷ
ﮏﯿﺗﺎﻣﻮﺳ ﺶﻬﺟ
PTENنﺎﻃﺮـﺳ رد
يﺎـﻫ
ﯽﻧﺎـﺴﻧا
يدﺪﻌﺘﻣ
ﭘ نﺎﻃﺮﺳ ﻪﻠﻤﺟ زا
.ﺖـﺳا هﺪـﺷ شراﺰـﮔ تﺎﺘـﺳوﺮ
فﺬﺣ ﻪﭼﺮﮔا
ﺶـﻬﺟ و ﺎﻫ
نژ رد هداد خر يﺎـﻫ
PTENرد
30
ﺖــﻓﺎﺑ ﺪـﺻرد
نﺎﻃﺮــﺳ ﻪــﯿﻟوا ﻞــﺣاﺮﻣ زا ﻞـﺻﺎﺣ يﺎــﻫ
و تﺎﺘﺳوﺮﭘ
63
ﺖﻓﺎﺑ ﺪﺻرد
و ﯽﯾﺎـﻬﺘﻧا ﻞﺣاﺮﻣ يﺎﻫ
ﺖـﺳد
يزاﺪﻧا
يﺮـﮕﯾد ﻞـﻣاﻮﻋ ﻪﺑ هزوﺮﻣا ﯽﻟو ،ﺖﺳا هﺪﺷ شراﺰﮔ
ﺰﯾر نﻮﭼ
RNAﻢﯿﻈﻨﺗ ناﻮﻨﻋ ﻪﺑ ﺰﯿﻧ ﺎﻫ
هﺪﻨﻨﮐ
زا ﺲـﭘ يﺎـﻫ
ﻪﻤﺟﺮﺗ
PTEN.ﺖﺳا هﺪﺷ هرﺎﺷا
) 25 و 26 (لﺎﺳ رد
2007
،
miR-21ﺰـﯾر ﻦﯿـﻟوا ناﻮـﻨﻋ ﻪﺑ
RNAفﺪــﻫ ﻪــﮐ ﺪــﺷ ﻪﺘﺧﺎﻨــﺷ
نآ ﻢﯿﻘﺘــﺴﻣ
PTENرد و دﻮــﺑ
نﺎﻃﺮﺳ
لﻮﻠﺳ
و يﺪـﺒﮐ يﺎﻫ
هدر
نآ ﻂﺒﺗﺮـﻣ ﯽﻟﻮﻠـﺳ يﺎـﻫ
.ﺪﺷ ﯽﻓﺮﻌﻣ
) 27 (هدر ﺮﺑ ﻪﻌﻟﺎﻄﻣ ﺎﺑ نارﺎﮑﻤﻫ و ﻮﯿﻟ
ﯽﻟﻮﻠﺳ يﺎﻫ
تﺎﺘﺳوﺮﭘ نﺎﻃﺮﺳ ﺎﺑ ﻂﺒﺗﺮﻣ
DU145ﻪـﺑ ﯽﻬﺑﺎـﺸﻣ ﺞﯾﺎـﺘﻧ ،
.ﺪـﻧدروآ ﺖﺳد
) 28 (ﯽـﻃ ﻦﯿـﻨﭽﻤﻫ
ﺮـﮕﯾد ﻖـﯿﻘﺤﺗ ﮏـﯾ
miR-19 ، miR-23b ، miR-26b
و
miR-92aﻪـــــﺑ
ﻢﯿﻈﻨﺗ ناﻮﻨﻋ
هﺪﻨﻨﮐ
نﺎـﯿﺑ ﺢﻄـﺳ يﺎﻫ
PTENرد
هدر
يﺎـﻫ
ﺰـﯾر ﻦﯾا .ﺪﻧﺪﺷ ﯽﻓﺮﻌﻣ تﺎﺘﺳوﺮﭘ نﺎﻃﺮﺳ ﯽﻟﻮﻠﺳ
RNAﺎـﻫ
راﺮﻗ فﺪﻫ ﺎﺑ ﺪﻧردﺎﻗ
نداد
PTENﯽﺘـﺳد ﻦﯿﯾﺎـﭘ فاﺪـﻫا و
نآ
ﻦﯿﻠﮑﯾﺎﺳ ﺪﻨﻧﺎﻣ
D1،
و ﺮـﯿﺜﮑﺗ ﺖﻤـﺳ ﻪﺑ ار ﯽﻟﻮﻠﺳ ﺮﯿﺴﻣ
دﺎﺠﯾا
.ﺪﻨﻨﮐ ﺖﯾاﺪﻫ نﺎﻃﺮﺳ
) 29 (ﺰﯾر
RNAمﺎﯿﭘ ﺮﯿﺴﻣ و ﺎﻫ
ﯽﻧﺎﺳر
MAPK/ERK:
مﺎﯿﭘ ﺮﯿﺴﻣ
نژﻮـﺘﯿﻣ ﺎـﺑ هﺪﺷ لﺎﻌﻓ زﺎﻨﯿﮐ ﻦﯿﺌﺗوﺮﭘ ﯽﻧﺎﺳر
(Mitogen-activated protein kinase, MAPK)
ﻪﺑ
يﺎﻫﺮﯿـﺴﻣ زا ﯽﮑﯾ ناﻮﻨﻋ
دﺎـﺠﯾا رد ﻞـﯿﺧد ﯽﻟﻮﻠـﺳ نورد
نﺎﻃﺮـﺳ
.ﺖـﺳا هﺪـﺷ ﻪﺘﺧﺎﻨـﺷ ﻒـﻠﺘﺨﻣ يﺎـﻫ
ﺮﯿـﺴﻣ ﻦـﯾا
مﺎﯿﭘ
ﺘﻨﮐ رد ﯽﻧﺎﺳر
دﺎﺠﯾا و لﻮﻠﺳ دﺪﻌﺘﻣ يﺎﻫﺪﻨﯾاﺮﻓ لﺮ
هﺪﻨﻨﮐ
،ﯽﻟﻮﻠﺳ ﺮﯿﺜﮑﺗ ﺪﻨﻧﺎﻣ نﺎﻃﺮﺳ
يﺎـﻘﺑ ،ﯽﻟﻮﻠـﺳ ﻪـﺧﺮﭼ ﻢﯿـﻈﻨﺗ
گر ،لﻮﻠــﺳ
ﯽﻟﻮﻠــﺳ تﺮﺟﺎــﻬﻣ و ﯽــﯾاز
ﺮﯿﺛﺄﺗ
.ﺖــﺳا راﺬــﮔ
لﺎﻌﻓ
يﺎﻫﺪـﻧﺎﮕﯿﻟ لﺎـﺼﺗا ﺎﺑ ﺮﯿﺴﻣ ﻦﯾا يزﺎﺳ
ﺪـﻨﻧﺎﻣ ﻂﺒﺗﺮـﻣ
هﺪﻧﺮﯿﮔ ﻪﺑ ﺪﺷر ﻞﻣﺎﻋ
ﺢﻄﺳ رد دﻮﺟﻮﻣ ﯽﯾﺎﺸﻏ ﻦﯾزوﺮﯿﺗ يﺎﻫ
و زﺎﻏآ لﻮﻠﺳ
ﺐﺒﺳ
ﺖﻔﺟ
هﺪﻧﺮﯿﮔ نﺪﺷ ﻪﻠﯾﺮﻔﺴﻓ و
ﯽﻣ
.دﻮﺷ
ﻦﯿﺌﺗوﺮﭘ ﺲﭙﺳ
2
ﻋ هﺪـﻧﺮﯿﮔ ﻪـﺑ هﺪﻧﻮـﺷ ﻞـﺼﺘﻣ
ﺎ
ﻞـﻣ
ﺪـﺷر
(Grb2)نآ لﺎﺒﻧد ﻪﺑ و
ﺾﯾﻮﻌﺗ ﻦﯿﺗوﺮﭘ ﮏﯾ
ﻦﯿﻧاﻮـﮔ هﺪﻨﻨﮐ
(SOS)ﯽﻣ هﺪﻧاﻮﺧاﺮﻓ
.ﺪﻧﻮﺷ
لﺎﻌﻓ رﺎﺸﺑآ
ﺚﻋﺎﺑ يزﺎﺳ
لﺎـﻌﻓ
ﺷ
ــــ
نﺪ
Ras ، Raf ، Mekو
ERKﯽﻣ
ﺷ
ـــ
.دﻮ
ERKﺐﺒـﺳ و دراو ﻪﺘـﺴﻫ ﻞﺧاد ﻪﺑ ﻪﻠﯾﺮﻔﺴﻓ
و نﺪـﺷ ﻪﻠﯾﺮﻔـﺴﻓ
لﺎﻌﻓ
ﻞﻣاﻮﻋ يزﺎﺳ
ﻪﺑ و ﯽﺴﯾﻮﻧور
ﺰﯾﺎـﻤﺗ و ﺮـﯿﺜﮑﺗ نآ لﺎﺒﻧد
ﯽﻣ لﻮﻠﺳ
.دﻮﺷ
) 30 (ﺰـﯿﻧ تﺎﺘﺳوﺮﭘ نﺎﻃﺮﺳ رد
ﺮﯾﺎـﺳ ﺪـﻨﻧﺎﻤﻫ
نﺎﻃﺮﺳ
مﺎـﯿﭘ ﺮﯿﺴﻣ نﺎﯿﺑ ﺶﯾاﺰﻓا ﺎﻫ
زﺎـﻨﯿﮐ ﻦﯿﺌﺗوﺮـﭘ ﯽﻧﺎـﺳر
لﻮـﻤﻌﻣ رﻮـﻃ ﻪـﺑ ﻪـﮐ هﺪـﺷ شراﺰﮔ نژﻮﺘﯿﻣ ﺎﺑ هﺪﺷ لﺎﻌﻓ
ﻦﯾا ﯽﻧﺎﯿﺑ تاﺮﯿﯿﻐﺗ
مﺎﯿﭘ ﺮﯿﺴﻣ ﯽﻧﺎﯿﺑ تاﺮﯿﯿﻐﺗ ﺎﺑ ﺮﯿﺴﻣ
ﯽﻧﺎـﺳر
ﺪﯿﺘﯾزﻮﻨﯾاﻮﻔﺴﻓ
3
ﺎـﻨﯿﮐ
ز
/
زﺎـﻨﯿﮐ ﻦﯿﺌﺗوﺮـﭘ
B
هدﻮـﺑ هاﺮـﻤﻫ
ﺖﺳا
.
) 31 (ﻪﻌﻟﺎﻄﻣ
ﺎـﺸﻧ ﺎﻫ
هداد ن
ﺪـﻧا
miR-143
ﮏـﯾ ﻪـﮐ
نﺎـﯿﺑ ﺶﻫﺎـﮐ تﺎﺘﺳوﺮﭘ نﺎﻃﺮﺳ رد ﺖﺳا رﻮﻣﻮﺗ هﺪﻨﻨﮐرﺎﻬﻣ
نآ فﺪﻫ نﺎﯿﺑ ﺶﯾاﺰﻓا ﺐﺒﺳ و دراد
،
ERK5ﯽﻣ
رد و دﻮﺷ
ﯽﻤﺟﺎـﻬﺗ رﺎﺘﻓر و ﺮﯿﺜﮑﺗ ﺖﻤﺳ ﻪﺑ لﻮﻠﺳ ﺖﯾﺎﻬﻧ
ﯽـﻣ
.دور
) 31 (ﻖﯿﻘﺤﺗ
هداد نﺎﺸﻧ ﺎﻫ
مﺎـﯿﭘ ﺮﯿﺴﻣ ﻦﯾا ﺪﻧا
ﻞـﺣاﺮﻣ رد ﯽﻧﺎـﺳر
ﻪﯿﻟوا
45
ﻪﺘﻓﺮﺸﯿﭘ ﻞﺣاﺮﻣ رد و ﺪﺻرد
90
تاﺮـﯿﯿﻐﺗ ﺪـﺻرد
نﺎﺸﻧ دﻮﺧ زا ﯽﻧﺎﯿﺑ
ﯽﻣ
ﻫد
ﺪ.
) 32 (ﺰﯾر
RNAمﺎﯿﭘ ﺮﯿﺴﻣ و ﺎﻫ
ﯽﻧﺎﺳر
WNT:
مﺎﯿﭘ يﺎﻫﺮﯿﺴﻣ زا ﺮﮕﯾد ﯽﮑﯾ
ﺮﺛﺆـﻣ ﯽﻧﺎـﺳر
نﺎﻃﺮـﺳ رد
ﺮﯿﺴﻣ تﺎﺘﺳوﺮﭘ
wnt.ﺖﺳا
ﻢﻫ ﺮﺛا
ﺰﻓا
ﻪـﺑ ﺮﯿـﺴﻣ ﻦـﯾا ﯽـﯾا
مﺎﯿﭘ ﺮﯿﺴﻣ هاﺮﻤﻫ
ﯽﻧﺎﺳر
Rasرد
ـﺸﯿﭘ
ﯽﯾﺎـﻬﺘﻧا ﻞـﺣاﺮﻣ دﺮﺒ
نﺎــﯿﺑ ﺶﯾاﺰــﻓا ﺎــﺑ تﺎﺘــﺳوﺮﭘ نﺎﻃﺮــﺳ
نژ
ﺪــﻨﻧﺎﻣ ﯽﯾﺎــﻫ
ژﺎﻧﮋﯿﺴﮐاﻮﻠﮑﯿﺳ
-2
و
c-Myc.ﺖﺳا هﺪﺷ شراﺰﮔ
) 33 (ﺑ
نﺎـﯿ
مﺎﯿﭘ يﺎﺠﺑﺎﻧ
ﯽﻧﺎـﺳر
wnt
يراﺪـﯾﺎﭘ ﺐﺒـﺳ
B-Cateninو
نآ دورو
ﻪـــﻋﻮﻤﺠﻣ ،نآ لﺎـــﺒﻧد ﻪـــﺑ و ﻪﺘـــﺴﻫ ﻪـــﺑ ﺎـــﻫ
B-catenin-TCF/LEF
نژ زا ﯽﺴﯾﻮﻧور ﺐﺒﺳ
فﺪﻫ يﺎﻫ
70 ﻦﯾوﺰﻗ ﯽﮑﺷﺰﭘ مﻮﻠﻋ هﺎﮕﺸﻧاد ﯽﻤﻠﻋ ﻪﻠﺠﻣ هرﺎﻤﺷ ،ﻢﺘﺴﯿﺑ لﺎﺳ ، 3 ﯽﭘ رد ﯽﭘ) 86 و دادﺮﻣ ،( ﻬﺷ رﻮﯾﺮ 1395 ﻪﻟﺎﻘﻣ / يروﺮﻣ
ﺪﻨﻧﺎﻣ دﻮﺧ
c-MYC،
c-jun،
ﻦﯿﻠﮑﯾﺎﺳ
D1و
يﺮﺗﺎﻣ
ﻦﯾﺰﯾﻻ
وﺮﭘﻮﻟﺎﺘﻣ
ﯽﻣ ﺎﻫزﺎﻨﯿﺌﺗ
.دﻮﺷ
ﺗ
ﻖـﯿﻘﺤ
ﺎـﻫ
هداد نﺎـﺸﻧ
نﺎـﯿﺑ ﺪـﻧا
MiR-34aرد
هدر
ﯽﻟﻮﻠــــﺳ يﺎــــﻫ
PC-3ﻂﯾاﺮــــﺷ رد
،ﯽﻫﺎﮕﺸﯾﺎﻣزآ
ﮑﺗ
ﯿﺜ
ﻢﺟﺎﻬﺗ و ﯽﻟﻮﻠﺳ ﺮ
ﻒﻗﻮﺘﻣ ار
لﻮﻠـﺳ و
ﺎـﻫ
ار
ﺖﻤﺳ ﻪﺑ
ﯽﻟﻮﻠﺳ گﺮﻣ
ﯽـﻣ ﺶﯿـﭘ
.دﺮـﺑ
) 33 (ﻦﯿـﻨﭽﻤﻫ
رد
ﻞﻘﺘﺴﻣ ﻪﻌﻟﺎﻄﻣ
ﺮﮕﯾد
miR-320ناﻮﻨﻋ ﻪﺑ
ﻢﯿـﻈﻨﺗ زا ﯽﮑﯾ
هﺪﻨﻨﮐ
يﺎﻫ
ﺮﯿﺴﻣ
wnt/b-cateninﻪﺘﺧﺎﻨﺷ
هﺪﺷ
ا
ﺖﺳ
.
) 34 (ﺰﯾر
RNAمﺎﯿﭘ ﺮﯿﺴﻣ و ﺎﻫ
ﯽﻧﺎﺳر
p53:
p53
رﻮﻣﻮﺗ هﺪﻨﻨﮐرﺎﻬﻣ ﮏﯾ
ﺖـﺳا
زا ﺶﯿـﺑ رد ﻪـﮐ
50
ﺪﺻرد
ﺎﻫرﻮﻣﻮﺗ عاﻮﻧا
،
ﺎﯾ ﺶﻬﺟ
ﺣ
زا ﺶﯿﺑ رد و ﯽﻧژ فﺬ
80
ﺪﺻرد
ﺎﻫرﻮﻣﻮﺗ
،
ﺮﺑ
ﺮﯿﺴﻣ ندرﻮﺧ ﻢﻫ
مﺎﯿﭘ
ﯽﻧﺎﺳر
شراﺰـﮔ نآ
.ﺖﺳا هﺪﺷ
) 35 (ﻣ
ﻌﻟﺎﻄ
ﻪ
ﺎﻫ
هداد نﺎﺸﻧ
ﺪﻧا
p53يﺎـﻘﻟا ﻪـﺑ ردﺎﻗ
نﺎﯿﺑ
ﺰﯾر
RNAﺎﻫ
ﯾ
رد ﻪﮐ ﺖﺳا ﯽ
ﺪـﻨﯾاﺮﻓ
ﻒـﻗﻮﺗ
ﯽﻟﻮﻠـﺳ
و
ﻪﻣﺎﻧﺮﺑ گﺮﻣ
لﻮﻠﺳ هﺪﺷ يﺰﯾر
ﺪﻧراد ﺶﻘﻧ
ﯽﻣ ﻪﮐ
نآ زا ناﻮﺗ
ﻪﺑ
ﻪﺷﻮﺧ
miR-15a/16-1 ، miR-145 ، miR-34و
Let-7.دﺮﮐ هرﺎﺷا
) 36 (ﺰﯾر
RNA:نﺪﺑ تﺎﻌﯾﺎﻣ رد دﻮﺟﻮﻣ يﺎﻫ
زا
آن
ﺎﺟ
ﻪﮐ
ﺰﯾر
RNAﯽﮑﭼﻮـﮐ هزاﺪﻧا و هﺎﺗﻮﮐ ﯽﻟاﻮﺗ ﺎﻫ
،ﺪﻧراد
ﺮﺑاﺮﺑ رد ًﺎﺘﺒﺴﻧ
ﺮﺛا
ﻢﯾﺰﻧآ
ﻪﯾﺰﺠﺗ
هﺪـﻨﻨﮐ
RNAموﺎـﻘﻣ
ﺪﻨﺘﺴﻫ
و
زا
ﺰﯾر
RNAﺖﻓﺎﺑ و مﺮﺳ رد دﻮﺟﻮﻣ يﺎﻫ
ﯽﻣ
ناﻮﺗ
ناﻮﻨﻋ ﻪﺑ
ﺖﺴﯾز
نﺎـﺸﻧ
ﺮـﮔ
ﺮـﮐ هدﺎﻔﺘـﺳا
.د
) 37 (ﻦﯿـﻨﭽﻤﻫ
زا
راردا ﻪﻧﻮﻤﻧ
ﺖـﻬﺟ تﺎﺘـﺳوﺮﭘ نﺎﻃﺮـﺳ ﻪـﺑ ﻼﺘـﺒﻣ نارﺎـﻤﯿﺑ
زا ﯽﺧﺮﺑ تاﺮﯿﯿﻐﺗ نﺎﯿﺑ ﯽﺳرﺮﺑ
ﺰـﯾر
RNAﺎـﺑ ﻂﺒﺗﺮـﻣ يﺎـﻫ
هﺪﺷ هدﺎﻔﺘﺳا تﺎﺘﺳوﺮﭘ نﺎﻃﺮﺳ
ﺖﺳا
ﮏـﯾ ناﻮـﻨﻋ ﻪـﺑ ﻪـﮐ
ﯽﻤﺟﺎﻬﺗﺮﯿﻏ ﻪﻧﻮﻤﻧ
ﻪﺑ
ﺶﯿﺑ ﯽﺳرﺮﺑ
ﺮـﺗ
زﺎـﯿﻧ ي
دراد
)
لوﺪـﺟ
هرﺎﻤﺷ
2
.(
) 38 و 40 (ﺶﯿﭘ يﺎﻫﺮﯿﻣ
بﻮﮐﺮﺳ /هﺪﻧﺮﺑ
:رﻮﻣﻮﺗ ﺮﮔ
ﺰــﯾر
RNAﺎــﻫ
سﺎــﺳاﺮﺑ ار
دﺮــﮑﻠﻤﻋ و نﺎــﯿﺑ تاﺮــﯿﯿﻐﺗ
ﯽﻣ
ناﻮـﺗ
هوﺮـﮔ ود ﻪـﺑ
دﺮـﮐ ﻢﯿـﺴﻘﺗ
هوﺮـﮔ :
لوا
يﺎـﻫﺮﯿﻣ
(ﺮﯿﻣﻮﮑﻧا) نژﻮﮑﻧا
ﺪﻨﺘﺴﻫ
ﯽـﻣ ﻪﮐ
ﮏـﯾ ناﻮـﻨﻋ ﻪـﺑ ﺪـﻨﻧاﻮﺗ
ﺶﯿﭘ
رﻮﻣﻮﺗ هﺪﻧﺮﺑ
ﮐ ﻞﻤﻋ
ﺪﻨﻨ
ﮏﯾ رﺎﻬﻣ ﺐﺒﺳ و
بﻮﮐﺮﺳ
ﺮـﮔ
رﻮﻣﻮﺗ
ﺪﻧﻮﺷ
.
نﺎﯿﺑ
ﺰـﯾر ﻦﯾا
RNAﺶﯾاﺰـﻓا نﺎﻃﺮـﺳ رد ﺎـﻫ
ﺰﯾر ،ﺮﮕﯾد هوﺮﮔ .دراد
RNAبﻮﮐﺮﺳ يﺎﻫ
ﺪﻨﺘـﺴﻫ رﻮﻣﻮﺗ ﺮﮔ
ﻪﮐ
نﺎﯿﺑ
نآ
ﺎﻫ
ﯽﻣ ﺶﻫﺎﮐ نﺎﻃﺮﺳ رد
ﺪﺑﺎﯾ
و
ﻪﺑ
رﻮﻃ
لﻮﻤﻌﻣ
ﻋﺎﺑ
ﺚ
ﯽﻔﻨﻣ ﻢﯿﻈﻨﺗ
نژ
ﺶﯿﭘ يﺎﻫ
رﻮـﻣﻮﺗ هﺪﻧﺮﺑ
نژ ﺎـﯾ
يﺎـﻫ
ﯽﻟﻮﻠﺳ گﺮﻣ هﺪﻨﻨﮐرﺎﻬﻣ
ﯽﻣ
ﺰﯾر ﻦﯾا .ﺪﻧﻮﺷ
RNAﺖـﺤﺗ ﺎـﻫ
ناﻮﻨﻋ
TSmiRsﯽﻣ ﻪﺘﺧﺎﻨﺷ
ﻮﺷ
ﻧﺪ
.
) 41 ( لوﺪﺟ 2 - ﺰﯾر RNA نﺎﻃﺮﺳ رد ﺮﮕﻧﺎﺸﻧ ﺖﺴﯾز ﺖﯿﻠﺑﺎﻗ ﺎﺑ يﺎﻫ تﺎﺘﺳوﺮﭘ ﻊﺟاﺮﻣ ﯽﻨﯿﻟﺎﺑ ﺖﯿﻤﻫا تﺎﺘﺳوﺮﭘ نﺎﻃﺮﺳ رد ﺶﻘﻧ هﺎﮕﯾﺎﺟ نﺎﯿﺑ تاﺮﯿﯿﻐﺗ هﺪﺷ ﯽﺳرﺮﺑ ﻪﻧﻮﻤﻧ RNAﺰﯾر 38 ﯽﻬﮔآﺶﯿﭘ رﻮﻣﻮﺗ هﺪﻧﺮﺑﺶﯿﭘ 17q23.1 ﺶﯾاﺰﻓا هﺪﺷ ﻪﻨﯿﻓارﺎﭘ ﺖﻓﺎﺑو مﺮﺳ MiR-21 38 ﺺﯿﺨﺸﺗ رﻮﻣﻮﺗ ﺮﮔبﻮﮐﺮﺳ 1p31.3/9p24.1 ﺶﻫﺎﮐ هﺪﺷ ﻪﻨﯿﻓارﺎﭘ ﺖﻓﺎﺑ MiR-101 38 ﺺﯿﺨﺸﺗ رﻮﻣﻮﺗهﺪﻧﺮﺑﺶﯿﭘ 2q35 ﺶﯾاﺰﻓا هﺪﺷ ﻪﻨﯿﻓارﺎﭘ ﺖﻓﺎﺑ MiR-375 38 ﺺﯿﺨﺸﺗ رﻮﻣﻮﺗ ﺮﮔبﻮﮐﺮﺳ 1q32.2 ﺶﻫﺎﮐ راردا MiR-205 38 ﯽﻬﮔآﺶﯿﭘ رﻮﻣﻮﺗ ﺮﮔبﻮﮐﺮﺳ 20q13.33/18q11.2 ﺶﻫﺎﮐ هﺪﺷ ﺰﯾﺮﻓ هزﺎﺗ ﺖﻓﺎﺑ MiR-1 38،39 ﯽﻬﮔآﺶﯿﭘ /ﺺﯿﺨﺸﺗ رﻮﻣﻮﺗ ﺮﮔبﻮﮐﺮﺳ 5q32 ﺶﻫﺎﮐ هﺪﺷ ﻪﻨﯿﻓارﺎﭘ ﺖﻓﺎﺑ MiR-143 40 ﺺﯿﺨﺸﺗ رﻮﻣﻮﺗ ﺮﮔبﻮﮐﺮﺳ 10q23.31 ﺶﻫﺎﮐ راردا MiR-107
ﻪﺠﯿﺘﻧ و ﺚﺤﺑ
:يﺮﯿﮔ
نآ زا
نژ ﻪــﮐ ﺎــﺟ
ﻞﮑــﺷ رد يدﺪــﻌﺘﻣ يﺎــﻫ
و يﺮــﯿﮔ
و ﺪﻧراد ﺶﻘﻧ تﺎﺘﺳوﺮﭘ نﺎﻃﺮﺳ ﺖﻓﺮﺸﯿﭘ
ﻪﺑ ﻪﺟﻮﺗ ﺎﺑ
ﺶـﻘﻧ
ﺰــﯾر ﯽــﻤﯿﻈﻨﺗ
RNAنژ رد ﺎــﻫ
ﺨﻣ يﺎــﻫ
ﺘ
ﻒــﻠ
رد ﻞــﯿﺧد
ﺪﻨﯾاﺮﻓ
دﺪﻌﺘﻣ يﺎﻫ
ﯽﺘـﺴﯾز
)
،ﯽﻟﻮﻠـﺳ ﻪـﺧﺮﭼ ،ﺮـﯿﺜﮑﺗ
گﺮـﻣ
ﯽﻟﻮﻠﺳ
و
لﺎـﯿﻠﺘﯿﭘا لﺎﻘﺘﻧا
-
(ﯽﻤﯿـﺸﻧاﺰﻣ
ﻦـﯾا
رﻮـﺼﺗ ﻦﯿـﻨﭼ
ﯽﻣ
دﻮﺷ
ﻪﮐ
ﺰﯾر
RNAياراد ﺎﻫ
ﺗﻮ
ـﻧا
ﯽﯾﺎ
نﺎـﺸﻧ ﺖـﺴﯾز
ﺮـﮔ
ﺮﻃ و ﯽﺼﯿﺨﺸﺗ
ﯽـﺣا
نﺎﻃﺮـﺳ نﺎـﻣرد رد وراد
.ﺪﻨﺘـﺴﻫ ﺎـﻫ
ﻦﯿﻨﭽﻤﻫ
ﺶﻘﻧ ﻞﯿﻟد ﻪﺑ
ﺰﯾر
RNAيﺎﻫﺮﯿـﺴﻣ ﻢﯿﻈﻨﺗ رد ﺎﻫ
مﺎﯿﭘ
ﯽﻧﺎﺳر
دﺪﻌﺘﻣ
رد ﻞﯿﺧد
تﺎﺘـﺳوﺮﭘ نﺎﻃﺮﺳ
،
ﺎـﺑ
ﯽـﺣاﺮﻃ
وراد
ﯽﻣ ﺮﺛﺆﻣ ي
ﺰﯾر نﺎﯿﺑ ﻞﯾﺪﻌﺗ ﻪﺑ ناﻮﺗ
RNAﻪـﺠﯿﺘﻧ رد و
مﺎــﯿﭘ ﺮﯿــﺴﻣ رد نآ زا ﻞــﺻﺎﺣ ﺪــﻣﺎﯿﭘ
ﯽﻧﺎــﺳر
ﮏــﻤﮐ
.دﺮــﮐ
ﺰﯾر
RNAﺎﻫ
شور ﻪـﺑ دﻮـﺧ دﺮـﮑﻠﻤﻋ ﻪـﺑ ﻪـﺟﻮﺗ ﺎـﺑ
يﺎـﻫ
ﺗوﺎـــﻔﺘﻣ
ﯽ
رد
ﯽـــﺣاﺮﻃ
وراد
ﻪـــﺑ
ﯽـــﻣ رﺎـــﮐ
.ﺪـــﻧور
) 42 و 43 (ﺰﯾر
RNAرد رﻮﻣﻮﺗ هﺪﻨﻨﮐرﺎﻬﻣ يﺎﻫ
ﺮﺜﮐا
نﺎﻃﺮﺳ
ﺶﻫﺎﮐ ﺎﻫ
ﺪــﻧراد نﺎــﯿﺑ
،
شور زا هدﺎﻔﺘــﺳا ﺎــﺑ ﻦﯾاﺮﺑﺎــﻨﺑ
يﺎــﺟ
ﯽــﻨﯾﺰﮔ
ﺰﯾر
RNAﺎﯾ
ﺰﯾر ﺪﯿﻠﻘﺗ
RNAﯽﻣ
نآ نﺎﯿﺑ ناﻮﺗ
ار ﺎﻫ
ﺶﯾاﺰﻓا
.داد
) 44 (ﺰﯾر
RNAﺮﯿﻣﻮﮑﻧا يﺎﻫ
ﺶﯿﭘ
هﺪﻧﺮﺑ
ﺶﯾاﺰـﻓا ياراد و
رد نﺎﯿﺑ
نﺎﻃﺮﺳ
و ﺪﻨﺘﺴﻫ
زا هدﺎﻔﺘـﺳا ﺎـﺑ
ﻢـﺴﯿﻧﻮﮔﺎﺘﻧآ
يﺎـﻫ
ﺰﯾر
RNAﺎﻫ
ﯽﻣ
نآ نﺎﯿﺑ حﻮﻄﺳ ناﻮﺗ
ار ﺎﻫ
داد ﺶﻫﺎـﮐ
ـﺑ .
ﻪ
ﯽﻣ رﻮﻈﻨﻣ ﻦﯾا
ﺐﯿﮐﺮﺗ زا ناﻮﺗ
يﺎﻫ
ياراد
اﺛ
ﯽﮔﺪـﻨﻨﮐرﺎﻬﻣ ﺮ
ﺎﺑ ﯽﺘﺑﺎﻗر
ﺰﯾر
RNAﺎﻫ
هدﺎﻔﺘﺳا
ﺎﺑ ﺎﯾ دﺮﮐ
دﺮﺑرﺎﮐ
لﻮﮑﻟﻮﻣ
يﺎﻫ
RNAﻪــﻠﺧاﺪﻣ
ﺮــﮔ
ﮏــﭼﻮﮐ
(siRNA)ﺖــﯿﻟﺎﻌﻓ زا ﻊﻧﺎــﻣ
ﺰﯾر
RNAدرﻮﻣ
.ﺪﺷ ﺮﻈﻧ
) 45 (ﯽﻃ
ﺖﻓﺮﺸﯿﭘ
ﺖـﺳد ﻪـﺑ يﺎـﻫ
رد هﺪﻣآ
ﻪﻧﺎﻣﺎﺳ
ﺶﯿـﺑ ﺖﯿﺳﺎﺴﺣ و ﯽﮔﮋﯾو ﺎﺑ لﺎﻘﺘﻧا يﺎﻫ
ﺮـﺗ
موزﻮﭙﯿﻟ زا هدﺎﻔﺘﺳا ﺪﻨﻧﺎﻣ
ـﮐ ﻦﯿـﻨﭽﻤﻫ و تارذﻮﻧﺎـﻧ ﺎـﯾ
ﺎ
دﺮﺑر
ﮐﺮﺗ
ﺐﯿ
ﺶﯿﺑ يراﺪﯾﺎﭘ ﺎﺑ ﯽﯾﺎﻫ
ﺮـﺗ
،
هزﺎـﺗ يﺎﻫﺪـﯿﻣا
ﺖـﻬﺟ يا
نﺎﻣرد
نﺎﻃﺮﺳ ﻦﯾﻮﻧ يﺎﻫ
ﺎﻫ
)
تﺎﺘﺳوﺮﭘ نﺎﻃﺮﺳ ﻪﻠﻤﺟ زا
(
ﺎـﺑ
ا
ﺰﯾر زا هدﺎﻔﺘﺳ
RNA.ﺖﺳا ﻪﺘﻓﺮﮔ ﻞﮑﺷ ﺎﻫ
ﯽﻃ
ﻪﻌﻟﺎﻄﻣ
لﺎـﺳ زا هﺪـﺷ مﺎـﺠﻧا يﺎﻫ
2002
ﺎـﺗ
نﻮﻨﮐ
ﺰﯾر
RNAﻔﻠﺘﺨﻣ يﺎﻫ
نﺎﻃﺮـﺳ ﺶﯾاﺪـﯿﭘ رد ﯽ
ﺎـﻫ
ﻪـﻠﻤﺟ زا
تﺎﺘﺳوﺮﭘ نﺎﻃﺮﺳ
هﺪـﺷ ﻪﺘﺧﺎﻨﺷ ﺮﺛﺆﻣ
ﺪـﻧا
.
) 45 (ﻪـﺑ ﻪـﺟﻮﺗ ﺎـﺑ
ﺺﯿﺨﺸﺗ
ﺰـﯾر ﻖـﯿﻗد
RNAﺎـﻫ
شور زا هدﺎﻔﺘـﺳا ﺎـﺑ
يﺎـﻫ
نآ يراﺪﯾﺎﭘ و ﯽﻟﻮﮑﻟﻮﻣ
ﻪﻧﻮﻤﻧ رد ﺎﻫ
،ﯽﺘـﺴﯾز ﻒـﻠﺘﺨﻣ يﺎـﻫ
ﺰﯾر ناﺪﻨﻤﺸﻧاد
RNAار ﺎﻫ
ﻪﻨﯾﺰﮔ
ﺖﻬﺟ ﯽﺒﺳﺎﻨﻣ
رد ﮏـﻤﮐ
نﺎــﻣرد و ﺺﯿﺨــﺸﺗ
تﺎﺘــﺳوﺮﭘ نﺎﻃﺮــﺳ
ﺮﯾﺎــﺳ رﺎــﻨﮐ رد
نﻮــﻣزآ
ﯽــﺼﯿﺨﺸﺗ يﺎــﻫ
لواﺪــﺘﻣ ﯽﻧﺎــﻣرد و
،
ﯽــﻓﺮﻌﻣ
هدﺮﮐ
ﻧا
.ﺪ
) 46 (ﻖﯿﻗد ﺺﯿﺨﺸﺗ هﺪﻨﯾآ رد ﺖﺳا ﺪﯿﻣا
نﺎﻣرد و ﺮﺗ
ﺮﺗﺪﻣآرﺎﮐ
ار تﺎﺘﺳوﺮﭘ نﺎﻃﺮﺳ
ﺰﯾر ﮏﻤﮐ ﺎﺑ
RNAﺪﻫﺎـﺷ ﺎﻫ
.ﻢﯿﺷﺎﺑ
:ﻊﺟاﺮﻣ
1. Chen R, Ren Sh, Yiu MK, Fai NC, Cheng WS, Ian LH, et al. Prostate cancer in Asia: A collaborative report. Asian Journal of Urology 2014 Oct; 1 (1): 15-29. doi: org/10. 1016/j.ajur.2014.08.0072. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin 2014 Jan-Feb; 64 (1): 9-29.
3. Hosseini M, SeyedAlinaghi S, Mahmoudi M, McFarland W. A case-control study of risk factors for prostate cancer in Iran. Acta Med Iran 2010 Jan-Feb; 48 (1): 61-6.
4. Daniyal M, Siddiqui ZA, Akram M, Asif HM, Sultana S, Khan A. Epidemiology, etiology, diagnosis and treatment of prostate cancer. Asian Pac J Cancer Prev 2014; 15 (22): 9575-8.
5. Leitzmann MF, Rohrmann S. Risk factors for the onset of prostatic cancer: age, location, and behavioral correlates. Clin Epidemiol 2012; 4: 1-11. doi: 10.2147/CLEP. S16747.
6. Center MM, Jemal A, Lortet-Tieulent J, Ward E, Ferlay J, Brawley O, et al. International variation in prostate cancer incidence and mortality rates. Eur Urol 2012 Jun; 61 (6): 1079-92. doi: 10.1016/j.eururo. 2012.02.054.
7. Hessels D, Schalken JA. Urinary biomarkers for prostate cancer: a review. Asian J Androl 2013 May; 15 (3): 333-9. doi: 10.1038/aja.2013.6.
72 ﻦﯾوﺰﻗ ﯽﮑﺷﺰﭘ مﻮﻠﻋ هﺎﮕﺸﻧاد ﯽﻤﻠﻋ ﻪﻠﺠﻣ هرﺎﻤﺷ ،ﻢﺘﺴﯿﺑ لﺎﺳ ، 3 ﯽﭘ رد ﯽﭘ) 86 و دادﺮﻣ ،( ﻬﺷ رﻮﯾﺮ 1395 ﻪﻟﺎﻘﻣ / يروﺮﻣ
et al. Roles and mechanism of miR-199a and miR-125b in tumor angiogenesis. PLoS One 2013; 8 (2): e56647. doi: 10.1371/journal. pone. 0056647.
17. Hilmarsdottir B, Briem E, Bergthorsson JT, Magnusson MK, Gudjonsson T. Functional role of the microRNA-200 family in breast morphogenesis and neoplasia. Genes (Basel) 2014 Sep 11; 5 (3): 804-20. doi: 10. 3390/genes5030804.
18. Siemens H, Jackstadt R, Hünten S, Kaller M, Menssen A, Götz U, et al. miR-34 and SNAIL form a double-negative feedback loop to regulate epithelial - mesenchymal transitions. Cell Cycle 2011 Dec 15; 10 (24): 4256-71. doi: 10.4161/cc.10.24.18552. 19. Peng Y, Liu YM, Li LC, Wang LL, Wu XL. microRNA‑503 inhibits gastric cancer cell growth andepithelial‑to‑mesenchymal transition. Oncol Lett 2014 Apr;7(4):1233-8. 20. Rojas F, Hernandez ME, Silva M, Li L, Subramanian S, Wilson MJ, et al. The oncogenic response to MiR-335 is associated with cell surface expression of membrane-type 1 matrix metalloproteinase (MT1-MMP) Activity. PLoS One 2015 Jul 23; 10 (7):
e0132026.doi:10.1371/journal.pone.0132026.
21. Georgantas RW 3rd, Streicher K, Luo X, Greenlees L, Zhu W, Liu Z, et al. MicroRNA-206 induces G1 arrest in melanoma by inhibition of CDK4 and Cyclin D. Pigment Cell Melanoma Res 2014 Mar; 27 (2): 275-86. doi: 10.1111/pcmr.12200. 22. Wu X, Liu T, Fang O, Leach LJ, Hu X, Luo Z. miR-194 suppresses metastasis of non-small cell lung cancer through regulating expression of BMP1 and p27(kip1). Oncogene 2014 Mar 20; 33 (12): 1506-14. doi: 10.1038/onc.2013.108.
23. Jackson BL, Grabowska A, Ratan HL. MicroRNA in prostate cancer: functional 8. Hao Y, Zhao Y, Zhao X, He C, Pang X,
Wu TC, et al. Improvement of prostate cancer detection by integrating the PSA test with miRNA expression profiling. Cancer Invest 2011 May; 29 (4): 318-24. doi: 10.3109/ 07357907.2011.554477.
9. Agrawal SN, Singh C, Mehta SS, Ghuman HS, Mehta GS, Sadana SK. Implications of prostate specific antigen and its molecular derivatives in the management of carcinoma prostate. International Journal of Scientific Study 2015 Jul; 3 (4): 159-64. doi: 10.17354/ ijss/2015/327
10. Goto Y, Kurozumi A, Enokida H, Ichikawa T, Seki N. Functional significance of aberrantly expressed microRNAs in prostate cancer. Int J Urol 2015 Mar; 22 (3): 242-52. doi: 10.1111/iju.12700.
11. Hata A, Lieberman J. Dysregulation of microRNA biogenesis and gene silencing in cancer. Sci Signal 2015 Mar 17; 8 (368): 1-11. doi: 10.1126/scisignal.2005825.
12. Hu W, Coller J. What comes first: translational repression or mRNA degradation? The deepening mystery of microRNA function. Cell Res 2012 Sep; 22 (9): 1322-4. doi: 10.1038/cr.2012.80.
13. Vincent K, Pichler M, Lee GW, Ling H. MicroRNAs, genomic instability and cancer. Int J Mol Sci 2014 Aug 20; 15 (8): 14475-91. doi: 10.3390/ijms150814475.
14. Reddy KB. MicroRNA (miRNA) in cancer. Cancer Cell Int 2015 Apr 2; 15: 38. doi: 10.1186/s12935-015-0185-1.
15. Polioudakis D, Abell NS, Iyer VR. miR-503 represses human cell proliferation and directly targets the oncogene DDHD2 by non-canonical target pairing. BMC Genomics 2015 Feb 5; 16: 40. doi: 10.1186/s12864-015-1279-9.
Fleming J, Fisher G, et al. Mir143 expression inversely correlates with nuclear ERK5 immunoreactivity in clinical prostate cancer. Br J Cancer 2013 Jan 15; 108 (1): 149-54. doi: 10.1038/bjc.2012.510.
32. Mulholland DJ, Kobayashi N, Ruscetti M, Zhi A, Tran LM, Huang J, et al. Pten loss and RAS/MAPK activation cooperate to promote EMT and metastasis initiated from prostate cancer stem/progenitor cells. Cancer Res 2012 Apr; 72 (7): 1878-89. doi: 10.1158/ 0008-5472. CAN-11-3132.
33. Chen WY, Liu SY, Chang YS, Yin JJ, Yeh HL, Mouhieddine TH, et al. MicroRNA-34a regulates WNT/TCF7 signaling and inhibits bone metastasis in Ras-activated prostate cancer. Oncotarget 2015 Jan 1; 6 (1): 441-57.
34. Hsieh IS, Chang KC, Tsai YT, Ke JY, Lu PJ, Lee KH, et al. MicroRNA-320 suppresses the stem cell-like characteristics of prostate cancer cells by downregulating the Wnt/beta-catenin signaling pathway. Carcinogenesis 2013 Mar; 34 (3): 530-8. doi: 10.1093/ carcin/bgs371.
35. Liu J, Zhang C, Feng Z. Tumor suppressor p53 and its gain-of-function mutants in cancer. Acta Biochim Biophys Sin (Shanghai) 2014 Mar; 46 (3): 170-9. doi: 10. 1093/abbs/gmt144
36. .Otsuka K, Ochiya T. Genetic networks lead and follow tumor development: microRNA regulation of cell cycle and apoptosis in the p53 pathways. Biomed Res Int 2014; 2014: 749724. doi: 10.1155/2014/ 749724.
37. Gupta SK, Ban C, Thum T. Circulating microRNAs as biomarkers and potential paracrine mediators of cardiovascular disease. Circ Cardiovasc Genet 2010Oct; 3(5): 484-8. doi: 10.1161/CIRCGENETICS.110.958363. importance and potential as circulating
biomarkers. BMC Cancer. 2014 Dec 10; 14: 930. doi: 10.1186/1471-2407-14-930.
24. Fendler A, Stephan C, Yousef GM, Jung K. MicroRNAs as regulators of signal transduction in urological tumors. Clin Chem 2011 Jul; 57 (7): 954-68. doi: 10.1373/ clinchem.2010.157727.
25. Shtivelman E, Beer TM, Evans CP. Molecular pathways andtargets in prostate cancer. Oncotarget 2014 Sep 15; 5 (17): 7217-59.
26. Fallahabadi ZR, Daloii MR, Mahdian R, Behjati F, Shokrgozar MA, Abolhasani M, et al. Frequency of PTEN alterations, TMPRSS2-ERG fusion and their association in prostatecancer.Gene2016 Jan10; 575(2 Pt 3): 755-60. doi: 10.1016/j.gene.2015.09. 068. 27. Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST, Patel T. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology 2007 Aug; 133 (2): 647-58.
28. Liu LZ, LiC, Chen Q, Jing Y, Carpenter R, Jiang Y, et al. MiR-21 induced angiogenesis through AKT and ERK activation and HIF-1α expression. PLoS One 2011 Apr 22; 6 (4): e19139. doi: 10.1371/ journal.pone.0019139.
29. Tian L, Fang YX, Xue JL, Chen JZ. Four microRNAs promote prostate cell proliferation with regulation of PTEN and its downstream signals in vitro. PLoS One 2013 Sep 30; 8 (9): e75885. doi: 10.1371/journal. pone.0075885.
30. Ito F. Target therapy for cancer: anti-cancer drugs targeting growth - factor signaling molecules. Biol Pharm Bull 2011; 34 (12): 1773.
74 ﻦﯾوﺰﻗ ﯽﮑﺷﺰﭘ مﻮﻠﻋ هﺎﮕﺸﻧاد ﯽﻤﻠﻋ ﻪﻠﺠﻣ هرﺎﻤﺷ ،ﻢﺘﺴﯿﺑ لﺎﺳ ، 3 ﯽﭘ رد ﯽﭘ) 86 و دادﺮﻣ ،( ﻬﺷ رﻮﯾﺮ 1395 ﻪﻟﺎﻘﻣ / يروﺮﻣ
by miR-23a and miR-23b in prostate cancer: computational and in vitro approaches. Tumour Biol 2015 Jun; 36 (6): 4203-12. doi: 10.1007/s13277-015-3057-3.
43. Nodouzi V, Nowroozi M, Hashemi M, Javadi Gh, Mahdian R, et al. Investigation of the changes in the expression levels of NKX3-1 and PTEN genes in clinical prostate cancer tissues.Genetics in the3rd Millennium. 2013; 11 (2): 3061-9. [In Persian]
44. Ling H, Fabbri M, Calin GA. MicroRNAs and other non-coding RNAs as targets for anticancer drug development. Nat Rev Drug Discov 2013 Nov; 12 (11): 847-65. doi: 10. 1038/nrd4140.
45. Joseph B, Nair VM. ONCMIRs: from bench to bed side. Asian J Pharm Clin Res 2013; 6 (1): 18-24.
46. Cannistraci A, Di Pace AL, De Maria R, Bonci D. MicroRNA as new tools for prostate cancer risk assessment and therapeutic intervention: results from clinical data set and patients' samples. Biomed Res Int 2014; 2014: 146170. doi: 10.1155/2014/146170. 38. Casanova-Salas I, Rubio-Briones J,
Fernandez-Serra A, López-Guerrero JA. miRNAs as biomarkers inprostate cancer. Clin Transl Oncol 2012 Nov; 14 (11): 803-11. doi: 10.1007/s12094-012-0877-0.
39. Peng X, Guo W, Liu T, Wang X, Tu X, Xiong D, et al. Identification of miRs-143 and -145 that is associated with bone metastasis of prostate cancer and involved in the regulation of EMT. PLoS One 2011; 6 (5): e20341. doi: 10.1371/journal.pone. 0020341.
40. Bryant RJ, Pawlowski T, Catto JW, Marsden G, Vessella RL, Rhees B, et al. Changes in circulating microRNA levels associated with prostate cancer. Br J Cancer 2012 Feb 14; 106 (4): 768-74. doi: 10.1038/ bjc.2011.595.
41. Babashah S. MicroRNAs: key regulators of oncogenesis. Springer; 2014. 3-28. doi: 10.1007/978-3-319-03725-7
42. Aghaee-Bakhtiari SH, Arefian E, Naderi M, Noorbakhsh F, Nodouzi V, Asgari M, et al. MAPK and JAK/STAT pathways targeted