Sankara
Epigenetics
Epigenetics: Ciwon daji epigenetics Matsayin tsakiya na lalacewar DNA da lahani na epigenetic a cikin kwayoyin gyaran DNA a cikin carcinogenesis Ra'ayi na gargajiya game da ciwon daji wani nau'in cututtuka ne waɗanda ke haifar da ci gaba na rashin daidaituwa na kwayoyin halitta waɗanda suka haɗa da maye gurbi a cikin ƙwayoyin cuta masu hana ƙari da oncogenes da rashin daidaituwa na chromosomal. Daga baya an gano rawar da aka samu na sauye-sauye na epigenetic.[92] Canje-canjen Epigenetic gyare-gyaren da suka dace da aiki zuwa ga kwayoyin halitta wadanda ba sa canza jerin nucleotide. Misalan irin wadannan gyare-gyare sune canje-canje a cikin DNA methylation (hypermethylation da hypomethylation), gyare-gyaren histone[93] da canje-canje a cikin gine-ginen chromosomal (wanda ya haifar da rashin dacewa na sunadaran kamar HMGA2 ko HMGA1).[94]. Kowane bayan waɗannan sauye-sauye yana sarrafa maganganun kwayoyin halitta ba tare da canza jerin DNA na asali ba. Waɗannan canje-canjen na iya wanzuwa ta hanyar rarrabuwar sel, suna dawwama ga tsararraki masu yawa kuma ana iya daukar su azaman epimutation (daidai da maye gurbi). Canje-canje na Epigenetic yana faruwa akai-akai a cikin ciwon daji. Alal misali, binciken daya ya lissafa kwayoyin halittar sunadaran sunadaran da aka saba canzawa akai-akai a cikin methylation tare da ciwon daji na hanji. Wadannan sun hada da 147 hypermethylated da 27 hypomethylated genes. Daga cikin kwayoyin halittar hypermethylated, 10 sun kasance hypermethylated a cikin 100% na ciwon daji na hanji kuma wasu da yawa sun kasance hypermethylated a cikin fiye da 50% na ciwon daji na hanji.[95]. Yayin da ake samun sauye-sauye na epigenetic a cikin ciwon daji, sauye-sauye na epigenetic a cikin kwayoyin gyaran DNA, yana haifar da raguwar maganganun sunadarai na gyaran DNA, na iya zama mahimmanci. Ana tsammanin irin waɗannan sauye-sauyen suna faruwa da wuri kafin su ci gaba zuwa cutar kansa kuma suna iya zama sanadin rashin zaman lafiyar kwayoyin halittar cututtukan daji.[96][97][98] Rage bayanin kwayoyin halittar DNA na gyaran DNA yana rushe gyaran DNA. Ana nuna wannan a cikin adadi a mataki na 4 daga sama. (A cikin adadi, jajayen kalmomi suna nuna tsakiyar rawar lalacewar DNA da lahani a cikin gyaran DNA don ci gaba zuwa ciwon daji.) Lokacin da gyaran DNA ya gaza lalacewar DNA ya kasance a cikin sel a matakin sama fiye da yadda aka saba (mataki na 5) kuma yana haifar da kara yawan mitoci. maye gurbi da/ko epimutation (matakin 6). Adadin maye gurbi yana karuwa sosai a cikin ƙwayoyin da ba su da lahani a cikin gyare-gyaren rashin daidaituwa na DNA[99] [100] ko a cikin gyaran hadin gwiwa (HRR).[101] Sabuntawar chromosomal da aneuploidy suma suna karuwa a cikin sel marasa lahani na HRR.[102] Mafi girman matakan lalacewa na DNA yana haifar da karar maye gurbi (gefen siffa na dama) da kara kazanta. Yayin gyaran DNA ninki biyu karya, ko gyara wasu lalacewar DNA, wuraren gyara da ba su cika cika ba na iya haifar da shiru na kwayoyin halitta.[103][104] Rashin bayyanar sunadaran gyaran DNA saboda maye gurbi na iya kara hadarin kansa. Mutanen da ke da nakasar gada a cikin kowane nau'in halittar DNA na 34 (duba labarin DNA gyara-rashi cuta) sun haɓaka haɗarin kansa, tare da wasu lahani suna tabbatar da damar 100% na ciwon daji (misali p53 maye gurbi).[105]. An lura da maye gurbi na gyaran layin DNA a gefen hagu na adadi. Duk da haka, irin wannan maye gurbi (wanda ke haifar da ciwon daji na ciwon daji) shine kawai ke haifar da kusan kashi 1 cikin dari na ciwon daji.[106] A cikin cututtukan daji na lokaci-lokaci, ƙarancin gyare-gyaren DNA na faruwa lokaci-lokaci ta hanyar maye gurbi a cikin kwayar halittar DNA amma galibi ana haifar da su ta hanyar sauye-sauyen epigenetic wadanda ke rage ko yin shuru na maganganun kwayoyin halittar DNA. An nuna wannan a cikin adadi a matakin 3rd. Yawancin binciken da aka yi na carcinogenesis mai nauyin ƙarfe mai nauyi ya nuna cewa irin waɗannan ƙananan karafa suna haifar da raguwa a cikin maganganun gyaran enzymes na DNA, wasu ta hanyar hanyoyin epigenetic. An ba da shawarar hana gyaran DNA don zama babbar hanyar da ke haifar da cutar sankara mai nauyi. Bugu da kari, akai-akai sauye-sauye na epigenetic na lambar jerin DNA don kananan RNAs da ake kira microRNAs (ko miRNAs). miRNAs ba sa kididdige sunadaran sunadaran, amma suna iya “nufa” ƙwayoyin furotin-coded kuma su rage maganganunsu. Ciwon daji galibi suna tasowa ne daga tarin maye gurbi da kwankwasa waɗanda ke ba da fa'idar zabin da ke haifar da haɓaka clonal (duba lahani na ci gaba zuwa kansa). Maye gurbi, duk da haka, bazai zama akai-akai a cikin cututtukan daji kamar sauye-sauyen epigenetic ba. Matsakaicin ciwon daji na nono ko hanji yana iya samun sauye-sauyen furotin da kusan 60 zuwa 70, wanda kusan uku ko hudu na iya zama maye gurbin “direba” sauran kuma na iya zama maye gurbin “fasinja”