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PLAC1

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PLAC1
Identifikatori
AliasiPLAC1
Vanjski ID-jeviOMIM: 300296 MGI: 1926287 HomoloGene: 11039 GeneCards: PLAC1
Lokacija gena (čovjek)
Hromosom X
Hrom.Hromosom X[1]
Hromosom X
Genomska lokacija za PLAC1
Genomska lokacija za PLAC1
BendXq26.3Početak134,565,838 bp[1]
Kraj134,764,322 bp[1]
Lokacija gena (miš)
Hromosom X (miš)
Hrom.Hromosom X (miš)[2]
Hromosom X (miš)
Genomska lokacija za PLAC1
Genomska lokacija za PLAC1
BendX A5|X 29.31 cMPočetak52,158,872 bp[2]
Kraj52,328,988 bp[2]
Obrazac RNK ekspresije
Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija• molekularna funkcija
Ćelijska komponenta• extracellular region
• ćelijska komponenta
Biološki proces• multicellular organism development
• Placentacija
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez

10761

56096

Ensembl

ENSG00000170965

ENSMUSG00000061082

UniProt

Q9HBJ0

Q9JI83

RefSeq (mRNK)

NM_021796
NM_001316887
NM_001316888
NM_001316889

NM_019538
NM_001357802

RefSeq (bjelančevina)

NP_001303816
NP_001303817
NP_001303818
NP_068568

NP_062411
NP_001344731

Lokacija (UCSC)Chr X: 134.57 – 134.76 MbChr X: 52.16 – 52.33 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

Placentnospecifični protein 1 je mali (212 aminokiselinski), sa ćelijske površine lučeći protein koji je kod ljudi kodiran genom PLAC1. Od otkrića 1999., utvrđeno je da PLAC1 ima ulogu u razvoju i održavanju placente, kontroliraju nekoliko gestacijskih poremećaja, uključujući preeklampsiju, razvoj fetusa i veliki broj kancera.

Genomika

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PLAC1 nalazi se na dugom kraku X-hromosoma, na poziciji Xq26.3. Gen se sastoji od šest egzona raspona gotovo 200Kb (GRCh38 / hgs38; X: 134,565,838 - 134,764,322). Čitava kodirajućsa sekvenca plus 3 ’UTR i dio 5’ UTR čine egzon 6, dok egzoni 1 - 5 sadrže različito spojene elemente ostatka 5’UTR, uključujući dva neovisno regulirana promotora. Ova dva promotora, nazvana P1 (distalni) i P2 (proksimalni), nalaze se u egzonima, 1 odnosno 4. Pokazalo se da istovremeno proizvode transkripte, iako transkripcija P1 prevladava u karcinomima, a P2 u placenti .[5]

Filogenetika

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Od svog početnog opisa konsenzus je da je PLAC1 visoko konzerviran i da to ima važnu ulogu u uspostavljanju i održavanju placente.[6]

Detaljna studija gena i proteina PLAC1 placente 54 vrste sisara, koji predstavljaju dvanaest krunskih redova potvrđuje visok nivo konzerviranosti pod kontrolom stroge pročišćavajuće selekcije. Dalje, uporedne genomske sekvence dvaju torbara, oposuma (Mondelphis domestica) i valabija ( Macropus eugenii ), monotremata, kljunara (Ornithorhynchus anatinus), dvije ptice, kokoš ( Gallus gallus) i zeba ( Taeniopygia guttata ), te dvije ribe, zebrica (Danio rerio) i gregorac (Gasterosteus aculeatus), u rasponu sintetske regije X-hromosoma iz PHD-prstovog proteina 6 (PHD6) do faktora 9 (F9) pregledana je na bilo koju 'PLAC1-oliku sekvencu. Pokazano je da se PLAC1 pojavio u životinjskom genomu istovremeno s pojavom sisara sa placentom (Placentalia) prije nekih 165 000 000 godina.

Funkcija

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Otkriće PLAC1 rezultat je ispitivanja regije oko gena ljudske hipoksantin-ribosiltransferaze 1 (HPRT) s ciljem utvrđivanja da li je tamo kodiran protein specifičan za placentu. Ovo je pitanje pokrenuto jer se vjerovalo da je regija uključena i u patologije placente i fetusa. Nađeno je da se identificirani PLAC1 i njegov mišji ortolog Plac1 eksprimiraju tokom trudnoće. Brzo je utvrđeno da je ekspresija PLAC1 specifična za ćelije trofoblasta i da je presudan element u uspostavljanju i održavanju normalne placente. Ekspresija je dalje lokalizirana na apikalnom području sinciciotrofoblasta, vodećeg, invazivnog dijela embriona u razvoju. Ekspresija PLAC1 prestaje početkom porođaja, a PLAC1 iRNK čiste periferni majčin cirkulacijski sistem ubrzo nakon porođaja.

Prepoznavanje da PLAC1 ima važnu ulogu u prvom uspostavljanju placente, a potom i u njenom održavanju tokom trudnoće dovodi do ideje da PLAC1 može imati ulogu u gestacijskim problemima, od neplodnosti do preranog porođaja. Važan doprinos ovoj ideji je zapažanje da je model nokaut miša Plac1 pokazao placentomegaliju u branama i ograničenje rasta kod mladunaca. Brojni gestacijski problemi povezani su s abnormalnom ekspresijom PLAC1, uključujući unutarmaternično ograničenje rasta (IUGR), prerano rođenje [7][8] , neuspjeh u implantaciji i preeklampsija.[9][10] Nekoliko ovih studija nastojalo je razviti PLAC1 testove u dijagnostičke alate sa mješovitim uspjehom.

Kancer

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Iako je jasno utvrđeno da je PLAC1 zaista specifičan za posteljicu, gotovo od samog početka bilo je jasno i da je kooptiran kod karcinoma kod ljudi. Prvi dokazi da je PLAC1 kooptiran za rak objavljeni su 2006. Od tada, ekspresija PLAC1 dokazana je u više od desetak ljudskih karcinoma i u najmanje stotinu ćelijskih linija tih karcinoma. Među karcinomima kod kojih je izražena ekspresija PLAC1 su karcinomi želuca[11][12] karcinomi debelog crijeva/debelog crijeva.[13][14], karcinomi jetre[15], karcinomi gušterače, karcinomi pluća i rak dojke. U gotovo svim slučajevima, ekspresija PLAC1 povezana je sa lošim kliničkim ishodima. Nigdje ovo nije tako kao kod karcinoma muškog i ženskog reproduktivnog trakta. Odnosno, rak prostate [16] rak maternice , rak jajnika i rak grlića maternice [55] pokazali su pozitivnu korelaciju između ekspresije PLAC1 i prognoze.

U 2005., pokazalo se da je ekspresija PLAC1 u diferenciranju fibroblasta regulirana njihovim faktorom rasta 7 (FGF7). Otada se pokazalo da je ovaj regulatorni odnos presudan za proliferaciju ćelija karcinoma posredovanu serin/ treonin kinazom . PLAC1 formira kompleks ćelijske površine sa FGF7 i receptorom FGFR2IIIb, koji zatim aktivira kaskadu koja dovodi do fosforilacije Akt-a. Ekspresija PLAC1 zauzvrat je djelomično određena supresijom tumora. Ekspresija PLAC1 potiskuje p53 divljeg tipa, ali se povećava u prisustvu mutiranog ili odsutnog.

Imunoterapija

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PLAC1 je klasificiran kao „antigen karcinoma testisa”, jer se preferencijalno izražava u trofoblastima i tumorima. Pored rezultata koji povezuju ekspresiju PLAC1 s rizikom od različitih karcinoma kao i s prognozom, sposobnost PLAC1 da izazove imunski odgovor sugerira da bi se njegova specifičnost mogla terapijski iskoristiti. Jedna grupa posebno prednjači u potencijalu.[17] Korištenjem konjugata anti-PLAC1/ lijek pokazali su da imunoterapija zasnovana na PLAC1 vrlo obećava .[18] Nejadmoghaddam MR, Zarnani AH, Ghahremanzadeh R, Ghods R, Mahmoudian J, Yousefi M, Nazari M, Ghahremani MH, Abolhasani M, Anissian A, Mahmoudi M, Dinarvand R. 2017 Placenta-specific1 (PLAC1) is a potential target for antibody-drug conjugate-based prostate cancer immunotherapy. Sci Rep. Oct 17;7(1):13373. doi: 10.1038/s41598-017-13682-9. PubMed

Reference

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000170965 - Ensembl, maj 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000061082 - Ensembl, maj 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Chen Y, Moradin A, Schlessinger D, Nagaraja R. 2011 RXRα and LXR activate two promoters in placenta- and tumor-specific expression of PLAC1. Placenta. Nov;32(11):877-84. doi: 10.1016/j.placenta. PubMed
  6. ^ Jackman SM, Kong X, Fant ME. 2012 Plac1 (placenta-specific 1) is essential for normal placental and embryonic development. Mol Reprod Dev. Aug;79(8):564-72. doi: 10.1002/mrd.22062. PubMed
  7. ^ Farina A, Rizzo N, Concu M, Banzola I, Sekizawa A, Grotti S, Carinci P. 2004 Lower maternal PLAC1 mRNA in pregnancies complicated with vaginal bleeding (threatened abortion <20 weeks) and a surviving fetus. Clin Chem. Jan;51(1):224-7. doi: 10.1373/clinchem.2004.041228. PubMed
  8. ^ Rizzo N, Banzola I, Concu M, Morano D, Sekizawa A, Giommi F, Vagnoni S, Gabrielli S, Tempesta A, Carinci P, Farina A. 2006 PLAC1 mRNA levels in maternal blood at induction of labor correlate negatively with induction-delivery interval. Eur J Obstet Gynecol Reprod Biol. Jun;132(2):177-81. PubMed
  9. ^ Fujito N, Samura O, Miharu N, Tanigawa M, Hyodo M, Kudo Y. 2006 Increased plasma mRNAs of placenta-specific 1 (PLAC1) and glial cells-missing 1 (GCM1) in mothers with pre-eclampsia. Hiroshima J Med Sci. Mar;55(1):9-15. PubMed
  10. ^ Levine L, Habertheuer A, Ram C, Korutla L, Schwartz N, Hu RW, Reddy S, Freas A, Zielinski PD, Harmon J, Molugu SK, Parry S, Vallabhajosyula P. 2020 Syncytiotrophoblast extracellular microvesicle profiles in maternal circulation for noninvasive diagnosis of preeclampsia. Sci Rep. Apr 14;10(1):6398. doi: 10.1038/s41598-020-62193-7. Sci Rep. 2020. PubMed
  11. ^ Otsubo T, Akiyama Y, Hashimoto Y, Shimada S, Goto K, Yuasa Y. 2011 MicroRNA-126 inhibits SOX2 expression and contributes to gastric carcinogenesis. PLoS One. Jan 27;6(1):e16617. doi: 10.1371/journal.pone.0016617.PLoS One. PubMed
  12. ^ Liu FF, Shen DH, Wang S, Ye YJ, Song QJ. 2010 [Expression of PLAC1/CP1 genes in primary colorectal carcinoma and its clinical significance]. Zhonghua Bing Li Xue Za Zhi. 2010 Dec;39(12):810-3. PubMed
  13. ^ Liu F, Shen D, Kang X, Zhang C, Song Q. 2015 New tumour antigen PLAC1/CP1, a potentially useful prognostic marker and immunotherapy target for gastric adenocarcinoma. J Clin Pathol. Nov;68(11):913-6. doi: 10.1136/jclinpath-2015-202978. PubMed
  14. ^ Guo L, Xu D, Lu Y, Peng J, Jiang L. 2017 Detection of circulating tumor cells by reverse transcription‑quantitative polymerase chain reaction and magnetic activated cell sorting in the peripheral blood of patients with hepatocellular carcinoma. Mol Med Rep. Nov;16(5):5894-5900. doi: 10.3892/mmr.2017.7372. PubMed
  15. ^ Wu Y, Lin X, Di X, Chen Y, Zhao H, Wang X. 2017 Oncogenic function of Plac1 on the proliferation and metastasis in hepatocellular carcinoma cells. Oncol Rep. Jan;37(1):465-473. doi: 10.3892/or.2016.5272. PubMed
  16. ^ Liu F, Zhang H, Shen D, Wang S, Ye Y, Chen H, Pang X, Song Q, He P. 2014 Identification of two new HLA-A*0201-restricted cytotoxic T lymphocyte epitopes from colorectal carcinoma-associated antigen PLAC1/CP1. J Gastroenterol. Mar;49(3):419-26. doi: 0.1007/s00535-013-0811-4. PubMed
  17. ^ Mahmoudian J, Nazari M, Ghods R, Jeddi-Tehrani M, Ostad SN, Ghahremani MH, Vafaei S, Amiri MM, Zarnani AH. 2020 Expression of Human Placenta-specific 1 (PLAC1) in CHO-K1 Cells. Avicenna J Med Biotechnol. 2020 Jan-Mar;12(1):24-31. PubMed
  18. ^ Ghods R, Ghahremani MH, Madjd Z, Asgari M, Abolhasani M, Tavasoli S, Mahmoudi AR, Darzi M, Pasalar P, Jeddi-Tehrani M, Zarnani AH. 2014 High placenta-specific 1/low prostate-specific antigen expression pattern in high-grade prostate adenocarcinoma. Cancer Immunol Immunother. Dec;63(12):1319-27. doi: 10.1007/s00262-014-1594-z. PubMed

Dopunska literatura

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  • Chen Y, Moradin A, Schlessinger D, Nagaraja R. 2011 RXRα and LXR activate two promoters in placenta- and tumor-specific expression of PLAC1. Placenta. Nov;32(11):877-84. doi: 10.1016/j.placenta. PubMed
  • Devor EJ. 2014 Placenta-specific protein 1 is conserved throughout the Placentalia under purifying selection. ScientificWorldJournal. 2014:537356. doi: 10.1155/2014/537356. PubMed Free PMC article.
  • Devor, EJ 2016 Placenta-specific protein 1 (PLAC1) is a unique onco-fetal-placental protein and an underappreciated therapeutic target in cancer. Integrative Cancer Sci Ther. 3: 479-483.
  • Chang WL, Wang H, Cui L, Peng NN, Fan X, Xue LQ, Yang Q. 2016 PLAC1 is involved in human trophoblast syncytialization. Reprod Biol. Sep;16(3):218-224. doi: 10.1016/j.repbio.2016.07.001. PubMed
  • Massabbal E, Parveen S, Weisoly DL, Nelson DM, Smith SD, Fant M. 2005 PLAC1 expression increases during trophoblast differentiation: evidence for regulatory interactions with the fibroblast growth factor-7 (FGF-7) axis. Mol Reprod Dev. Jul;71(3):299-304.PubMed
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  • Fant M, Weisoly DL, Cocchia M, Huber R, Khan S, Lunt T, Schlessinger D. 2002 PLAC1, a trophoblast-specific gene, is expressed throughout pregnancy in the human placenta and modulated by keratinocyte growth factor. Mol Reprod Dev. Dec;63(4):430-6. PubMed
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  • Fant ME, Fuentes J, Kong X, Jackman S. 2014 The Nexus of Prematurity, Birth Defects, and Intrauterine Growth Restriction: A Role for PLAC1-Regulated Pathways. Front Pediatr. Feb 21;2:8. eCollection 2014. Review. PubMed
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  • Sifakis S, Androutsopoulos VP, Pontikaki A, Velegrakis A, Papaioannou GI, Koukoura O, Spandidos DA, Papantoniou N. 2018 Placental expression of PAPPA, PAPPA-2 and PLAC-1 in pregnancies is associated with FGR. Mol Med Rep. May;17(5):6435-6440. doi: 10.3892/mmr.2018.8721. PubMed
  • Ibanoglu MC, Ozgu-Erdinc AS, Kara O, Topcu HO, Uygur D. 2019 Association of Higher Maternal Serum Levels of Plac1 Protein with Intrauterine Growth Restriction. Z Geburtshilfe Neonatol. Oct;223(5):285-288. doi: 10.1055/a-0743-7403. PubMed
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  • Kodama M, Miyoshi H, Fujito N, Samura O, Kudo Y. 2011 Plasma mRNA concentrations of placenta-specific 1 (PLAC1) and pregnancy associated plasma protein A (PAPP-A) are higher in early-onset than late-onset pre-eclampsia. J Obstet Gynaecol Res. Apr;37(4):313-8. doi: 10.1111/j.1447-0756.2010.01349.x. PubMed
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  • ] Ibanoglu MC, Ozgu-Erdinc AS, Uygur D. 2018 Maternal placi protein levels in early- and late-onset preeclampsia. Ginekol Pol. 89(3):147-152. doi: 10.5603/GP.a2018.0025. PubMed
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  • Liu W, Zhai M, Wu Z, Qi Y, Wu Y, Dai C, Sun M, Li L, Gao Y. 2012 Identification of a novel HLA-A2-restricted cytotoxic T lymphocyte epitope from cancer-testis antigen PLAC1 in breast cancer. Amino Acids. Jun;42(6):2257-65. doi: 10.1007/s00726-011-0966-3. PubMed
  • Liu F, Zhang H, Shen D, Wang S, Ye Y, Chen H, Pang X, Song Q, He P. 2014 Identification of two new HLA-A*0201-restricted cytotoxic T lymphocyte epitopes from colorectal carcinoma-associated antigen PLAC1/CP1. J Gastroenterol. Mar;49(3):419-26. doi: 0.1007/s00535-013-0811-4. PubMed
  • Yin Y, Zhu X, Huang S, Zheng J, Zhang M, Kong W, Chen Q, Zhang Y, Chen X, Lin K, Ouyang X. 2017 Expression and clinical significance of placenta-specific 1 in pancreatic ductal adenocarcinoma. Tumour Biol. Jun;39(6):1010428317699131. doi: 10.1177/1010428317699131.Tumour Biol. 2017. PubMed
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  • Wagner M, Koslowski M, Paret C, Schmidt M, Türeci O, Sahin U. 2013 NCOA3 is a selective co-activator of estrogen receptor α-mediated transactivation of PLAC1 in MCF-7 breast cancer cells. BMC Cancer. Dec 4;13:570. doi: 10.1186/1471-2407-13-570. PubMed

[47] Li Q, Liu M, Wu M, Zhou X, Wang S, Hu Y, Wang Y, He Y, Zeng X, Chen J, Liu Q, Xiao D, Hu X, Liu W. 2018 PLAC1-specific TCR-engineered T cells mediate antigen-specific antitumor effects in breast cancer. Oncol Lett. Apr;15(4):5924-5932. doi: 10.3892/ol.2018.8075. PubMed

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