Kuningi okwenzekile ezakhiweni zofuzo kusukela ngawo-1950 lapho ososayensi abadumile uWatson noCrick bethola isakhiwo se-DNA. Ngama-1960, ososayensi bathola ukuthi kunezibalo eziningi ze-DNA yabantu phakathi kwama-genes 'amahle,' futhi kwakuqukethe ukulandelana okuphindaphindiwe okuthiwa i-junk DNA-junk, ngomqondo wokuthi abacwaningi ngaleso sikhathi babengenakuqonda ukuthi yini ikhodi yayenzelwe.
Ukucwaninga ngeminyaka yama-1970 kubonise ukuthi ukulandelana okuningi okungabhalwanga kwamakhodi nakho kutholakala ngaphakathi kwezakhi zofuzo, ukuphazamisa izifunda zeprotheni-coding. Ingabe zonke lezi zinto zakhi zofuzo zazingenangempela ngempela? Vele akunjalo! Kwakuvele kubonakala sengathi yizingqondo ezingazi ukuthi zenzeni nayo ngaleso sikhathi.
Yini Ngempela E-DNA Yethu?
Kuvela ukuthi amaphesenti angaba ngu-5 kuphela e-DNA yomuntu empeleni ahlanganisa iphrotheni, ngokulinganiselwa. Ngakho ososayensi kusukela emashumini eminyaka adlule, amaphesenti angu-95 e-DNA ayengabhekwa njengento engafanele.
Kuthiwani ngo-2016, 2017, nangaphezulu? Uma kuziwa kwi-DNA yabantu, kusekhona nendawo encane engafakiwe, engaziwa. Noma kunjalo, i-microRNA yayikutholwa okubalulekile futhi okuqondene neziguli zomdlavuza ngezindlela ezihlukahlukene.
Iyini i-MicroRNA (i-miRNA)?
Kungenzeka ukuthi wezwa nge-RNA yesithunywa esikolweni esiphakeme esikolweni. Yilelo molekyu umzimba wakho usebenzise ukwenza amaprotheni amasha futhi wakhiwa usebenzisa i-DNA njengesifanekiso.
Futhi, ifundwa yi-ribosomes ngesenzo seprotheyini, noma ukuhumusha, ukwenza iphrotheni entsha.
I-Micro-RNA iyindlela ehlukile. I-MicroRNA, noma i-miRNA, ihlobo lwe-RNA elingahloswe ukuba lihlelwe iphrotheni. Empeleni kuncane kakhulu-ikhodi elandelana kakhulu-kunokulandelana okucacile okutshela umzimba ukuthi ukwakhiwa kanjani amaprotheni, njenge-insulin, isibonelo.
Ngakho uma ingekho ikhodi yeprotheyini, yimuphi umsebenzi wayo? I-MiRNA isebenza ukulawula izakhi zofuzo ngokusebenzisa izinqubo ezibizwa ngokuthi 'i-RNA siling' kanye 'nomthetho wokuthunyelwa kwezokuthutha kwesiginja.' La magama achazwa kancane kancane ngezansi.
Indima ye-MiRNA eCanscer
Ukutholakala kwe-miRNAs nezinye i-RNA ezingekho-coding kunezimpikiswano eziningi ezibalulekile-kanti ezinye zazo zingase zibheke ikakhulukazi ezigulini zomdlavuza ezifana nalabo abane-malmatancies ye-hematologic.
Ama-MiRNA anethonya lawo ngokulawula ukuthi umzimba wakho uhamba kanjani kusuka ku-DNA kuya ku-RNA amaprotheni. Lapho amaprotheni ezithakazelisayo ephenduka iphrotheni ehlobene nomdlavuza noma isakhi esitholakala ezindleleni ezibalulekile zomdlavuza, leyo mithetho ye-miRNA ingase ibe nendima ebalulekile.
Ama-miRNA amaningi ahlukene aye abikwa ukuthi ayaphuma, noma ngokwemigomo yesayense, ehlukunyezwa, kuziguli ezinezinhlobo ezahlukene zomdlavuza. Emangqamuzaneni omdlavuza, la ma-IRR akuzona ngaphansi komthethonqubo ofanele obonwe kumaseli aphilile, ngakho-ke amazinga angavamile we-miRNA kanye nezimpendulo ezingavamile zeselula zingabangela. Lokhu okubhekwa ngama-miRNA kufanele kuholele ekutheni i-miRNA ihilelekile ekwakhiweni komdlavuza nasekuthuthukisweni komdlavuza, uma iqalile.
I-MiRNA yaqale yaqondwa ngokwemigomo eminingi yesifo somdlavuza noma i-prototypes malignancies kubandakanya i-lymphocytic leukemia (CLL ) engapheli , i-myeloma (MM), i-T-cell lymphoma kanye ne-mantle cell lymphoma. Eqinisweni, insimu ye-miRNA emdlalweni yaqala ngempela lapho iqembu lezocwaningo libonisa ukuthi ama-miRNAs-miR-15 ne-miR-16-ayengxenye ye-chromosome evame ukulahleka noma isuswe ku-leukemia engapheli.
Ama-Signatures we-MiRNA
Kusukela ngaleso sikhathi, abacwaningi bebelokhu besebenza "emasayinini e-miRNA" - okungukuthi, amaphrofayili ahlukene wezinga le-miRNA eliphakeme noma elincishisiwe elingase lifane nesimo esithile somdlavuza owanikwa.
Isibonelo, isignesha ethile ye-miRNA ingase ihlotshaniswe nokuziphatha okunomdlavuza okunonya. Uma isetshenziswe ngale ndlela, amasignesha ama-miRNA nawo ngezinye izikhathi abizwa ngokuthi yi-biomarkers.
I-MiRNA ku-Treatment of Cancer
Indima ye-miRNA ekwelapheni komdlavuza njengamanje ibhekwa njengokwanelisayo, ngomqondo wokuthi izindlela zokwelapha ezintsha nezengcono zingabhekwa kangcono ezigulini ezifanele zisebenzisa amasignesha e-miRNA. Umbono owodwa wesikhathi esizayo wukuthi udokotela wakho angase akwazi ukusho into ethi: "Umdlavuza wakho unesignesha ye-miRNA ehlotshaniswa nemiphumela ethuthukisiwe nale nqubo entsha yokwelashwa, ngakho-ke singase sithole ukukhetha lokhu ukwelashwa okucatshangelwe ngokujulile."
Abacwaningi babheka ukuthi kungenzeka ukuthi basebenzise ama-RNA amancane njenge "abacindezeli bezinkinga" ngokubenza bahambe ngqo ngaphakathi kwamangqamuzana omdlavuza. Ama-MiRNA kanye namanye ama-RNA angewona amakhodi afana nokulandelana okufushane kakhulu, okwenza ukuba bafezelele inqubo ebizwa ngokuthi i-transfection, esebenzisa amagciwane ukuvala ukulandelana kokudlala.
Esinye isithakazelo mayelana nokusetshenziswa kwe-miRNAs ukukhomba lawo maseli omdlavuza aphikisana ne-chemotherapy noma i-radiation. Ngisho nalapho ukwelashwa okuvamile kuvimbela ngaphezu kwamaphesenti angu-98 wamangqamuzana omdlavuza, noma yikuphi okubizwa ngokuthi umdlavuza usulela amangqamuzana - amangqamuzana omdlavuza ekufihlekeni - asele angabangela ukuphindaphinda. Uma amangqamuzana omdlavuza angabhekwa nge-miRNAs noma amanye ama-RNA angenayo ikhodi, eyedwa noma ehlanganiswe nezinye izindlela zokwelapha, lokhu kuzoba ukuthuthukiswa kokwelapha. Ukuhlolwa kwemitholampilo kusetshenziswa i-miRNA yokwelapha isifo somdlavuza wesibindi nomdlavuza wamaphaphu usuvele ushicilelwe, nakuba kunezifundo eziningi ezidingekayo.
I-MiRNA ku-CLL
ENtshonalanga, i- CLL yi-leukemia evame kakhulu kubantu abadala. Ukuguqulwa okuvamile kwe-chromosomal ehambisana ne-CLL ukususwa kwengxenye ye-chromosome 13. Yini engase ikwazi ukuthi izakhi zofuzo zibaluleke kangaka ukuthi ukususwa kwayo kuholele emdlalweni? Leli DNA elahlekile litholakala ukuthi lihambisana ne-miRNAs. Lokhu kubangela ukucabanga ukuthi i-miRNA emibili ikakhulukazi - okuthiwa i-miR-15a ne-miR-16-1 ingase ihileleke njengesenzakalo sokuqala ekuthuthukiseni i-CLL.
Futhi ku-CLL - ngaphezu kwengxenye ekhona ekuthuthukiseni umdlavuza - i-miRNA ingaba neqhaza ekwenzeni imithi yamakhemikhali. Ukumelana no-fludarabine, umuthi we-chemo, uye wahlotshaniswa nezinguquko kumazinga amabili ama-RNA amancane okuthiwa i-miR-18, i-miR-22 ne-miR-21.
I-MiRNA ku-Myeloma eminingi
Eminyakeni yamuva, abacwaningi baye baqaphela ukuthi i-miRNA isichazwe ngokuhlukile kubantu abane- myeloma noma MM.
Eqinisweni, iqembu labacwaningi-Pichiorri kanye nabo osebenza nabo-baye basebenzisa lokho okuyaziwa ngama-signature e-miRNA ukuze bafake izimpawu ezihlukahlukene ze-myeloma . Iseli le-plasma liyingqamuzana legazi elimhlophe elingawenza izifo ze-antibodies, futhi lo mndeni wamaseli-ilungu lomndeni we-B-lymphocyte-uthola umdlavuza kuMM. Ama-myelomas amaningi angathuthuka kusuka esimweni esibucayi esibizwa ngokuthi i-monoclonal gammopathy yokubaluleka okungakahleleki (MGUS), futhi leli qembu lokucwaninga lithola umehluko njengoba uqhubeka kusuka esitokisini esisempilweni ye-plasma ukuze ubhekane ne-MGUS, ku-MM, ukulimala okuphelele.
Ngonyaka ka-2008, uPhihiorri kanye nozakwethu babika umbiko we-miRNA ophelele wezingqamuzana ezivamile ze-plasma, i-MGUS, ne-MM. Ubufakazi obukhulayo bubonisa ukuthi i-miRNA isebenza kahle njengabalawuli bokuthuthukiswa kwamaseli ngenkathi umzimba wenza amangqamuzana egazi enempilo , noma ngesikhathi ejwayelekile, i-hematopoiesis enempilo; kodwa ukuthi izinguquko ze-miRNA zingabandakanyeka noma zingase zihambisane nezinye izinguquko endleleni yokugula. Ukusetshenziselwa ukukhubazeka kwama-miRNAs kuye kwahlotshaniswa ne-myeloma eminingi engozini enkulu.
I-Ultraviolet Light ne-MiRNA ku-Melanoma
Ama-MiRNA angasetshenziselwa ukusiza ekukhanyeni ukuthi umuntu unomdlavuza. Ucwaningo lwamuva luhlobanise ukuxhuma phakathi kwe-ultraviolet ukuvezwa kwemisebe nokuthuthukiswa kwe-melanoma kumavolontiya abasha abesifazane. Amadoda ayisishiyagalombili anempilo , anemikhono enempilo ephakathi kweminyaka engu-31 no-38 ayalinganiswa namantombazane ayisishiyagalolunye anenhliziyo enempilo eneminyaka engama-35 kuya ku-46 ubudala abesebenze i-melanoma .
Ama-melanocytes yiwo amangqamuzana enza i-melanin, i-pigment yethu yabantu, okubangela izinto ezifana nezinwele, isikhumba nombala. Ama-melanocytes nawo amangqamuzana anomdlavuza e-melanoma. Ekucwaningweni, ukuvezwa kwesikhumba emisebeni ye-UV kuphakamisa ibhalansi ye-miRNA inkulumo ejwayelekile yamangqamuzana omzimba we-melanocyte-kodwa lezi zinguquko ze-miRNA ezenziwe yi-UV zihluke kakhulu phakathi kwabesifazane abanempilo nalabo abanomlando we-melanoma esikhathini esidlule, okuphakamisa ukuthi ama-melanocytes athile abantu, nakuba bebonakala bejwayelekile, sebevele bephendula ngokuhlukile emisebeni ye-UV, engase ichaze ingozi yabo yokuthuthukiswa komdlavuza wesikhathi esizayo.
Ngokuthakazelisayo, ama-melanocytes abantu abaphilile, lapho bevuleka emisebeni efanayo ye-UV, awazange abonise lezi zinguquko. Lokhu okutholakele okubaluleke kakhulu kuncike ekukhulumeni kwe-RNA kungasiza ososayensi ukuba baqonde kangcono indlela i-melanoma eqala ngayo nokuthi ingavikelwa kanjani, kanye nokugqugquzela imibono emisha yocwaningo kanye namasu wokwelapha.
Imithombo
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Pichiorri F, De Luca L, Aqeilan RI. Ama-microRNA: Abadlali abasha ku-Myeloma eminingi. Imingcele yeziGenetics . 2011; 2: 22.
Sha J, Gastman BR, uMorris N, et al. Impendulo ye-microRNAs kwi-UVR yelanga emanoranocyte ahlala esikhumba ahluke phakathi kweziguli ze-melanoma nabantu abanempilo. PLoS ONE 2016; 11 (5): e0154915. i-doi: 10.1371 / iphephandaba.pone.0154915.
Segura MF, Greenwald HS, uHanniford D, et al. I-MicroRNA ne-melanoma enomuthi: kusukela ekutholeni ukubikezela kanye nokwelapha. I-carcinogenesis . 2012; 33: 1823-1832.