UT MD Anderson masana kimiyya sun nuna TAp63 yana kashe ƙwayar cutar kansa
UT MD Anderson masana kimiyya sun nuna TAp63 yana kashe ƙwayar cutar kansa
Anonim

An daɗe da rufe p53, sanannen ɗan'uwanta mai hana ƙari, kwayar p63 tana yin aiki mai ƙarfi, muhimmin aiki na hana yaduwar cutar kansa zuwa sauran gabobin, masu bincike a Jami'ar Texas MD Anderson Cancer Center rahoton a cikin Oktoba 21 fitowar na Nature..

Ba wai kawai takamaiman nau'i na furotin p63 ke toshe metastasis ba, amma yana yin haka ta hanyar kunna enzyme Dicer, wanda ke taka muhimmiyar rawa wajen ƙirƙirar micro RNAs, ƙananan raƙuman RNA waɗanda ke tsara tarin hanyoyin salula.

"p63 shine babban mai kula da metastasis, muhimmiyar rawa a kansa, amma kafin yanzu, babu wanda ya fahimci yadda aka tsara Dicer," in ji babban marubuci Elsa R. Flores, Ph.D., Mataimakin Farfesa a Sashen MD Anderson. Kwayoyin Halitta da Kwayoyin Oncology.

Matsayin tsakiya na Dicer a cikin ƙa'idar miRNA yana nuna haɗin p63-Dicer mai yuwuwa yana da fa'ida mai nisa ga sauran hanyoyin salula, in ji Flores. Dicer, kamar yadda sunansa ke nunawa, yana yanka guda guda na RNA marasa coding wanda zai iya murkushe ko canza codeing RNA wanda ke gaya wa injin samar da furotin ta tantanin halitta abin da furotin zai yi.

Har ila yau, ƙungiyar ta nuna cewa p63 tana kunna miRNA ɗaya wanda kuma yana hana haɓakar ƙwayar cuta da metastasis. Cutar sankarau tana da kusan kashi 85 na duk mace-mace daga cutar kansa.

Nazarin da suka gabata sun nuna cewa mutant p53, wanda aka fi samu a cikin ciwon daji na ɗan adam, yana hana p63. "Abubuwan da muka gano sun nuna cewa sake kunna TAp63 a cikin ciwace-ciwacen da ba su da alamun TAp63 ko kuma a cikin wadanda ke bayyana p53 na mutant zai iya amfanar marasa lafiya da cutar ta metastatic," in ji Flores.

Lokacin da TAp63 ya ɓace, metastasis ya biyo baya

Gaskiya mai daure kai game da p63 ita ce cewa an cika ta a wasu ciwace-ciwace kuma ba a bayyana shi a wasu ba. Flores ya bayyana bambancin ya dogara da wane nau'i na furotin da aka samar. Sunadaran TAp63 ya haɗa da yanki da ke da mahimmanci don kunna abubuwan da ke cikin ƙasa wanda ke kare kwayoyin halitta daga lalacewar DNA. Siga na biyu wanda ya rasa wannan yanki na TA yana aiki da p53, p63 da p73 kuma yana da alaƙa da ci gaban kansa.

Masu binciken sun yi nazari kan rawar TAp63 ta hanyar haɓaka nau'ikan beraye waɗanda ba su da kwafin kwayoyin halittar TAp63 da sauran waɗanda ke da guda ɗaya kuma ɗayan da aka buga. Sun gano:

* Mice da ba su da kofe ɗaya ko duka biyu na TAp63 ba tare da bata lokaci ba sun haɓaka carcinomas (ciwon daji da ke farawa a kan epithelium, ko rufi, na gabo, mafi yawan nau'in ƙwayar ƙwayar cuta) da sarcomas, ciwace-ciwacen ƙashi, mai, guringuntsi. Wadannan ciwace-ciwacen ciwace-ciwace akai-akai zuwa hanta, huhu da kwakwalwa, kamar yadda ake yawan gani a cikin ciwon daji na ɗan adam.

* Mice da ba su da guda ɗaya ko duka kwafin p53 suna haɓaka ciwace-ciwacen ƙwayar cuta. Berayen da suka yi asarar kwafi ɗaya kowanne na p53 da TAp63 sun sami ciwuka da cutar kansa.

* Mice ba tare da kwafi na p53 gene waɗanda ba su da ɗaya ko biyu kofe na TAp63 sun haɓaka carcinomas da sarcomas sosai.

Tawagar ta gano cewa berayen da ba su da kwafin TAp63 guda ɗaya kawai suna da ciwace-ciwacen ciwace-ciwace fiye da ɓeraye waɗanda ba su da kwafin biyun. Binciken nasu yayi kama da bincike na baya-bayan nan da wasu suka yi wanda ke nuni da cewa asarar Dicer yana da irin wannan tasiri - yana da muni idan kwafin kwayar halitta daya ba ta aiki.

Ciwon daji masu girma suna da ƙananan matakan TAp63, Dicer da miR-130b

Sun kwatanta matakan magana na TAp63, Dicer, da kuma micro RNA miR-130b mai hana ƙari a cikin adadi mai yawa na samfuran kai da wuyan ɗan adam, huhu da kansar nono kuma sun gano cewa ciwace-ciwacen ƙwayoyi masu girma sun bayyana ƙananan matakan duka ukun.

Ƙarin gwaje-gwajen ya nuna cewa TAp63, amma ba p53 ba, yana ɗaure zuwa yankin mai gabatarwa na Dicer gene, inda zai iya kunna maganganun Dicer enzyme. Sake bayyana Dicer a cikin ƙananan ƙwayoyin TAp63 sun toshe ikon ƙwayoyin tumo don ƙaura da mamayewa, yana nuna cewa TAp63 yana hana mamayewa ta hanyar tsarin Dicer.

Hakazalika, masu binciken sun gano cewa TAp63 yana ɗaure ga mai tallan miR-130b da kuma sake bayyana Dicer da miR-130b a cikin sel marasa ƙarancin TAp63 yana haifar da mafi girman hana metastasis. "Wannan yana nuna cewa TAp63 yana daidaita duka Dicer da miR-130 don murkushe metastasis," in ji Flores.

Flores da abokan aiki suna binciken yadda sauran isoform na p63, deltaNp63, ke shafar ci gaban kansa da metastasis. Manufar ita ce fahimtar hanyoyin p63 isoforms a cikin ciwon daji don inganta maganin da aka yi niyya ga marasa lafiya tare da sauye-sauye a cikin hanyar p53 / p63.

Iyalin kwayoyin halitta suna aiki tare

Flores da abokan aiki suna nazarin kwayoyin p53, p63 da p73. "Babban burinmu shine mu fahimci yadda iyali ke aiki gaba ɗaya," in ji Flores. Misali, p53 na taka muhimmiyar rawa wajen sa ido kan kwafi tantanin halitta da kuma ba da odar sel da ba a iya gyarawa su kashe kansu. Lokacin da aka dakatar da p53, kamar yadda yake a cikin cututtuka da yawa, ƙwayoyin da ba su da lahani suna karuwa, suna haifar da cutar.

Koyaya, hanyoyin kwantar da hankali da aka tsara don sake kunna p53 ba sa aiki. "Dalilin da ya sa hanyoyin kwantar da hankali suka gaza shine ba sa la'akari da dukan iyalin," in ji Flores. A cikin wata takarda ta Nature da ta gabata, Flores da abokan aiki sun nuna p53 ba za su iya yin odar mummunan tantanin halitta don kashe kanta ba tare da p63 da p73 suma suna aiki.

Shahararren taken