Reprimo-like (RPRML) is a vertebrate gene located at human chromosome 17q21.32. It is a member of the Reprimo gene family which consists of two human-related protein-coding and intronless genes: Reprimo (RPRM) and RPRML. [1] Although poorly characterized, this lineage has been implicated in important developmental and cancer processes. [2]
Function
RPRML is normally expressed during the embryonic development of zebrafish. [3] Knocking down RPRML in this model, increases caspase-3 activity in the hemogenic endothelium, hindering the formation of hematopoietic precursor/stem cells and impairing definitive hematopoiesis. [4]
In humans, RPRML protein expression has been reported in the cytoplasm of glandular and foveolar epithelial cells of the stomach. [5] Analyses of multiple gastric tumors show its expression is significantly downregulated when compared to normal adjacent tissues. This loss of expression is associated with a reduction of the apoptotic marker cleaved caspase-3 and with a worse prognosis of patients with advanced stages of the disease. [5] RPRML overexpression in gastric cancer cell lines inhibits cell cycle progression at the G2/M phase, reduces cell proliferation, clonogenic capacity, and anchorage-independent growth. [5] Hence, it has been proposed as a novel tumor suppressor gene. In colorectal cancer cells, RPRML is a target of Wnt/β- catenin signaling pathway. [6] Further research is warranted to fully elucidate its biological function.
Similar to its homolog RPRM, the silencing of RPRML in gastric cancer is mediated by DNA methylation. Circulating methylated RPRML DNA in plasma samples has been successfully explored as a non-invasive biomarker for gastric cancer diagnosis. [5]
References
- ^ Wichmann, Ignacio A.; Zavala, Kattina; Hoffmann, Federico G.; Vandewege, Michael W.; Corvalán, Alejandro H.; Amigo, Julio D.; Owen, Gareth I.; Opazo, Juan C. (2016-10-10). "Evolutionary history of the reprimo tumor suppressor gene family in vertebrates with a description of a new reprimo gene lineage". Gene. 591 (1): 245–254. doi: 10.1016/j.gene.2016.07.036. ISSN 1879-0038. PMID 27432065.
- ^ Amigo, Julio D.; Opazo, Juan C.; Jorquera, Roddy; Wichmann, Ignacio A.; Garcia-Bloj, Benjamin A.; Alarcon, Maria Alejandra; Owen, Gareth I.; Corvalán, Alejandro H. (2018-06-25). "The Reprimo Gene Family: A Novel Gene Lineage in Gastric Cancer with Tumor Suppressive Properties". International Journal of Molecular Sciences. 19 (7): 1862. doi: 10.3390/ijms19071862. ISSN 1422-0067. PMC 6073456. PMID 29941787.
- ^ Figueroa, Ricardo J.; Carrasco-Avino, Gonzalo; Wichmann, Ignacio A.; Lange, Martin; Owen, Gareth I.; Siekmann, Arndt F.; Corvalán, Alejandro H.; Opazo, Juan C.; Amigo, Julio D. (2017). "Reprimo tissue-specific expression pattern is conserved between zebrafish and human". PLOS ONE. 12 (5): e0178274. Bibcode: 2017PLoSO..1278274F. doi: 10.1371/journal.pone.0178274. ISSN 1932-6203. PMC 5451059. PMID 28562620.
- ^ Stanic, Karen; Reig, German; Figueroa, Ricardo J.; Retamal, Pedro A.; Wichmann, Ignacio A.; Opazo, Juan C.; Owen, Gareth I.; Corvalán, Alejandro H.; Concha, Miguel L.; Amigo, Julio D. (9 May 2019). "The Reprimo gene family member, reprimo-like (rprml), is required for blood development in embryonic zebrafish". Scientific Reports. 9 (1): 7131. Bibcode: 2019NatSR...9.7131S. doi: 10.1038/s41598-019-43436-8. ISSN 2045-2322. PMC 6509255. PMID 31073223.
- ^ a b c d Alarcón, María Alejandra; Olivares, Wilda; Córdova-Delgado, Miguel; Muñoz-Medel, Matías; de Mayo, Tomas; Carrasco-Aviño, Gonzalo; Wichmann, Ignacio; Landeros, Natalia; Amigo, Julio; Norero, Enrique; Villarroel-Espíndola, Franz (2020-12-12). "The Reprimo-Like Gene Is an Epigenetic-Mediated Tumor Suppressor and a Candidate Biomarker for the Non-Invasive Detection of Gastric Cancer". International Journal of Molecular Sciences. 21 (24): 9472. doi: 10.3390/ijms21249472. ISSN 1422-0067. PMC 7763358. PMID 33322837.
- ^ Zhu, Chi; Yamaguchi, Kiyoshi; Ohsugi, Tomoyuki; Terakado, Yumi; Noguchi, Rei; Ikenoue, Tsuneo; Furukawa, Yoichi (April 2017). "Identification of FERM domain-containing protein 5 as a novel target of β-catenin/TCF7L2 complex". Cancer Science. 108 (4): 612–619. doi: 10.1111/cas.13174. ISSN 1349-7006. PMC 5406541. PMID 28117551.