Zambiri zakhala zikuchitika m'ma genetic kuyambira m'ma 1950 pamene asayansi otchuka Watson ndi Crick anapeza mmene DNA imachitira. M'zaka za m'ma 1960, asayansi adapeza kuti DNA yambiri inalipo pakati pa maonekedwe a 'majini', ndipo anali ophatikiza mobwerezabwereza mwazinthu zomwe zimatchedwa DNA, zopanda pake, chifukwa chakuti ochita kafukufuku panthawiyo sankamvetsa zomwe chikhocho chinali choyimira.
Kafukufuku m'zaka za m'ma 1970 adasonyeza kuti njira zambiri zopanda zolembera zinapezedwanso m'magazi, kusokoneza zigawo za mapuloteni. Kodi zonsezi ndizosafunikira kwenikweni? Inde sichoncho! Zinangowoneka ngati ndi maganizo omwe sankadziwa zoyenera kuchita panthawiyo.
Kodi Zomwe Zili M'kati mwa DNA Yathu?
Zili choncho kuti pafupifupi asanu pa zana aliwonse a DNA ya munthu amalowa mkati mwa mapuloteni, malinga ndi chiwerengero. Choncho kwa asayansi zaka makumi angapo zapitazo, 95 peresenti ya DNA idzaonedwa ngati yopanda kanthu.
Nanga bwanji 2016, 2017, ndi kupitirira? Pankhani ya DNA yaumunthu, palinso malo ena osadziwika, osadziŵika. Komabe, microRNA inali yofunika kwambiri ndipo ina yothandiza odwala khansa m'njira zambiri.
Kodi MicroRNA (miRNA) ndi chiyani?
Mwinamwake mwamvapo za bizinesi ya RNA ku sekondale. Ndilo molecule yomwe thupi lanu limagwiritsa ntchito popanga mapuloteni atsopano ndipo amapangidwa pogwiritsa ntchito DNA monga chithunzi.
Komanso, amawerengedwa ndi ribosomes pogwiritsa ntchito mapuloteni, kapena kumasulira, kupanga mapuloteni atsopano.
Micro-RNA ndi yosiyana kwambiri. MicroRNA, kapena miRNA, ndi mtundu wa RNA umene sungakonzedwenso kukhala puloteni. Ndizochepa kwambiri - ndondomeko yochepa kwambiri-yosiyana kwambiri ndi zomwe zimafotokozera thupi momwe angamangire mapuloteni, monga insulini, mwachitsanzo.
Tsono ngati sichilembera puloteni, kodi imagwira ntchito yanji? Chabwino, MiRNA imayesetsa kuyendetsa majini pogwiritsa ntchito njira zotchedwa 'RNA silencing' ndi 'kulembedwa kwaseri kwa lamulo la jini.' Mawu awa akufotokozedwa pang'ono pansipa.
Udindo wa MiRNA mu Khansa
Kupezeka kwa miRNAs ndi ma RNA ena omwe sali olembetsa ali ndi zofunikira zambiri-ndipo zina mwa izo zingakhale zogwirizana kwambiri ndi odwala khansa monga omwe ali ndi matenda oopsa a khansa.
MiRNAs imakhudza momwe thupi lanu limachokera ku DNA kupita ku RNA ndi mapuloteni. Pamene mapuloteni a chidwi amakhala ngati mapuloteni okhudzana ndi khansa kapena kampani yomwe imapezeka mu njira zazikulu za khansa, ndiye kuti malamulo a MiRNA angathe kukhala ndi gawo lalikulu.
Mitundu yambiri ya miRNA yakhala ikudziwika kuti ndi yowopsa, kapena mwa sayansi, yosokonezedwa, kwa odwala omwe ali ndi mitundu yosiyanasiyana ya khansa. M'maselo a khansa, maRNAswa sali pansi pa malamulo oyenerera omwe amawoneka m'maselo abwino, choncho magawo osadziwika a miRNAs ndi mayankho osadziwika a ma selo amatha. Mfundo imeneyi yokhudza miRNAs iyenera kutsogolera kuganiza kuti miRNA imakhudzidwa ndi chitukuko cha khansara komanso momwe khansa ikuyendera, kamodzi kayamba.
MiRNA poyamba inamvetsetsedwa mwa mitundu yambiri ya khansa kapena mafilimu omwe amachititsa kuphatikizapo matenda aakulu a khansa ya m'magazi (CLL ), multipleeloma (MM), t-cell lymphoma yodula komanso selo lymphoma. Ndipotu munda wa kansa wa kansa unayambira pamene gulu lofufuza linasonyeza kuti miRNAs-miR-15 ndi miR-16-inali mbali ya chromosome imene imatayika kapena imachotsedwa ku matenda aakulu a khansa ya m'magazi.
Miyina ya MiRNA
Kuyambira nthaŵi imeneyo, ofufuza akhala akugwira ntchito "signature miRNA" - ndiko kuti, mbiri zosiyana za miRNA zomwe zingakhale zizindikiro za khansara yopatsidwa.
Mwachitsanzo, chizindikiro cha miRNA chingakhale chogwirizana ndi khalidwe loopsa la khansa. Pogwiritsidwa ntchito mwanjira iyi, ma signature a miRNA amakhalanso otchedwa biomarkers.
MiRNA mu Chithandizo cha Khansa
Udindo wa miRNA mu chithandizo cha khansa tsopano ukuonedwa ngati wothandizira, chifukwa chakuti mankhwala atsopano ndi abwino angathe kuwunikira bwino kuti odwala agwiritse ntchito mayina a miRNA. Chiwonetsero chimodzi cha tsogolo ndi chakuti dokotala wanu akhoza kunena monga: "Khansara yanu ili ndi siginecha ya miRNA yomwe ikugwirizana ndi zotsatira zabwino ndi dongosolo latsopano la mankhwala, kotero ife tikhoza kufuna kupereka chithandizo cha mankhwalawa mozama kwambiri."
Ochita kafukufuku akuyang'ananso kuti angathe kugwiritsa ntchito tizilombo ta RNA monga "zotupa zoteteza thupi" mwa kuwalola kuti apite mwachindunji mkati mwa maselo a khansa. MiRNAs ndi ma RNA ena omwe sali olembetsa ndizowonongeka kwambiri, zomwe zimapangitsa iwo kukhala angwiro pa njira yotchedwa transfection, yomwe imagwiritsa ntchito mavairasi kutsegula zotsatirazo.
Mbali ina yokondweretsedwa yokhudzana ndi kugwiritsidwa ntchito kwa miRNAs ndiyo kuwongolera ma selo a khansa omwe sagwirizana ndi chemotherapy kapena radiation. Ngakhale pamene mankhwala ochiritsira amatha kupitirira 98 peresenti ya maselo a khansa, chirichonse chomwe chimatchedwa kuti khansa imayambira maselo - maselo a khansa kubisala - otsala angayambitse kubwereza. Ngati maselo a khansa yowonongeka angayang'ane ndi miRNAs kapena ma RNA omwe sali olemba, okha kapena kuphatikizapo njira zina zothandizira, izi zikhoza kuwonetseratu chithandizo chamankhwala. Mayesero a chipatala pogwiritsa ntchito miRNA therapeutically kwa khansa ya chiwindi ndi khansa ya m'mapapo yakhala ikufalitsidwa, ngakhale kuti maphunziro ambiri akufunika.
MiRNA mu CLL
Kumadzulo, CLL ndi khansa ya m'magazi ambiri mwa anthu akuluakulu. Kusintha kwakukulu kwa chromosomal yogwirizana ndi CLL ndiko kuchotsedwa kwa gawo la chromosome 13. Kodi chidziwitso cha chibadwa chingakhale chofunika bwanji kuti kuchotsedwa kwake kumabweretsa khansa? Chabwino, DNA iyi ikusowa inapezeka kuti ikutsamira kwa miRNAs. Izi zikuwongolera ku lingaliro lakuti miRNA iwiri makamaka - yotchedwa miR-15a ndi miR-16-1 ikhoza kuchitidwa monga chochitika choyambirira pakukula kwa CLL.
Komanso mu CLL - kuwonjezera pa zomwe zingatheke kuti chitukuko chitheke - miRNAs ikhoza kukhala ndi gawo la mankhwala a chemotherapy. Kukaniza kwa fludarabine, mankhwala osokoneza bongo, wakhala akugwirizana ndi kusintha kwa magawo awiri a RNA omwe amatchedwa miR-18, miR-22 ndi miR-21.
MiRNA mu Multiple Myeloma
M'zaka zaposachedwapa, ofufuza apeza kuti miRNAs imafotokozedwa mosiyana ndi anthu omwe ali ndi myeloma kapena MM.
Ndipotu, gulu la ofufuza-Pichiorri ndi anzake-agwiritsira ntchito zomwe zimadziwika pa zilembo za miRNA kuti ziwonetse maonekedwe osiyanasiyana a myeloma . Selo ya m'magazi ndi selo loyera la magazi lomwe lingapangitse ma antibodies, ndipo banja ili la maselo-membala wa banja la B-lymphocyte-limakhala ndi khansa mu MM. Mitundu yambiri ya myelomas ikhoza kukhala ndi matenda osokoneza bongo otchedwa monoclonal gammopathy ofunika kwambiri (MGUS), ndipo gulu lofufuzirali limapeza kusiyana komwe mukupita kuchokera ku selo labwino la plasma kuti likhale labwino koma MGUS, mwachangu, mankhwala osokoneza bongo.
Mu 2008, Pichiorri ndi anzake adalengeza mafotokozedwe a miRNA ofotokoza maselo ofanana a plasma, MGUS, ndi MM. Umboni wochuluka umasonyeza kuti miRNA imagwira ntchito bwino ngati olamulira opanga maselo pamene thupi limapanga maselo abwino a magazi , kapena pa nthawi zonse, hematopoiesis yathanzi; koma kusintha kwaMRNA kungaphatikizepo kapena kumaphatikizana ndi kusintha kwina kwa njira yopweteka. Kulephera kugwiritsidwa ntchito kwa miRNAs kunayanjananso ndi myeloma yambiri yoopsa.
Ultraviolet Kuwala ndi MiRNA mu Melanoma
MiRNAs ingagwiritsidwenso ntchito kuthandiza kuthandizira kuzindikira kuti munthu ali ndi khansa. Kafukufuku waposachedwapa anafufuza kugwirizana pakati pa kuwala kwa dzuwa ndi kusungunuka kwa khansa ya atsikana odzipereka. Amayi asanu ndi atatu ali ndi thanzi labwino kwambiri , omwe ali ndi zaka zapakati pa 31 ndi 38 anafanizidwa ndi akazi asanu ndi anayi okwana zaka 35 mpaka 46 omwe ali ndi khungu labwino kwambiri lomwe lakhala ndi melanoma .
Ma Melanocyte ndiwo maselo omwe amachititsa kuti tizilombo toyambitsa matenda a melanin, mtundu wathu wa anthu, omwe amachititsa zinthu ngati tsitsi, khungu ndi maso. Melanocyte ndi maselo omwe amakhala khansa mu khansa ya melanoma. Kufufuza, kufalikira kwa khungu kumayendedwe a UV kumapangitsa kuti miRNA iwonongeke m'maselo a mtundu wa melanocyte. Koma kusintha kumeneku kwasinthidwa pakati pa amayi ndi amayi omwe ali ndi mbiri ya khansa ya m'magazi m'mbuyomu, kutanthauza kuti ma melanocyte anthu, ngakhale kuti amawoneka ngati abwinobwino, amavomereza kale mazira a UV, omwe angafotokoze chiopsezo chawo cha kukula kwa khansa m'tsogolo.
N'zochititsa chidwi kuti ma melanocyte a anthu abwino, atakhala ndi mazira ofanana a UV, sanawonetse kusintha kumeneku. Zotsatirazi zomwe zimadalira kwambiri za micro-RNA mawu angathandize asayansi kumvetsetsa momwe chiwindi chimayambira ndi momwe chingatetezedwe, komanso kuti apangitse maganizo atsopano a kafukufuku ndi njira zothandizira.
Zotsatira
Portin P. Kubadwa ndi chitukuko cha DNA chiphunzitso cha cholowa: zaka makumi asanu ndi limodzi kuchokera pamene adapeza kapangidwe ka DNA. J Genet. 2014; 93 (1): 293-302.
Moussay E, Palissot V, Vallar L, et al. Kutsimikiza kwa majini ndi microRNA zomwe zimakhudza kukana fludarabine mu vivo mu matenda aakulu a khansa ya m'magazi. Khansa ya m'magazi. 2010; 9: 115.
Pichiorri F, De Luca L, Aqeilan RI. MicroRNAs: Osewera Chatsopano mu Myeloma Yambiri. Malire mu Genetics . 2011; 2: 22.
Sha J, Gastman BR, Morris N, et al. Kuyankha kwa microRNA kwa UVR dzuwa mu melanocyte khungu-okhala pakati pa odwala khansa ndi anthu wathanzi. PLoS ONE 2016; 11 (5): e0154915. lembani: 10.1371 / magazini.pone.0154915.
Segura MF, Greenwald HS, Hanniford D, et al. MicroRNA ndi melanoma ya cutaneous: kuchokera kufukufuku wopanga matenda ndi mankhwala. Carcinogenesis . 2012; 33: 1823-1832.