{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nResearch in familial pancreatic ductal adenocarcinoma has revealed that germline truncating mutations in RABL3 can predispose individuals to cancer, likely through dysregulation of RAS signaling. In these cases, the truncated RABL3 protein interacts with the chaperone RAP1GDS1 to accelerate KRAS prenylation, thereby promoting cell proliferation and even linking to developmental RASopathy syndromes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn non‐small cell lung cancer, high levels of RABL3 expression correlate with poor patient survival. Functional studies indicate that overexpressed RABL3 contributes to tumor cell survival by repressing MAPK8/9/10-mediated autophagy, thereby inhibiting cell death."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nInvestigations in hepatocellular carcinoma have shown that RABL3 is significantly upregulated in tumor tissues compared to adjacent normal liver. Elevated RABL3 expression is associated with features of advanced disease, including lymph node metastasis and portal vein invasion, while its experimental silencing results in reduced cancer cell proliferation and growth."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn several cancer cell models, RABL3 functions as an oncogene by enhancing proliferation, migration, and invasion, while concurrently inhibiting apoptosis and contributing to chemoresistance (e.g. against paclitaxel). These effects have been mechanistically linked to increased phosphorylation of focal adhesion kinase (FAK) and subsequent activation of protein kinase B (Akt), underscoring its role in modulating key oncogenic signaling pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional regulatory layers have been identified in gastrointestinal and oral malignancies. In gastric cancer, the circular RNA circCOL1A1 functions as a molecular sponge for miR-145, thus de-repressing RABL3 and promoting tumor cell proliferation, migration, and invasion. Similarly, serum and tissue analyses in oral squamous cell carcinoma indicate that RABL3 is markedly overexpressed and may serve as a promising biomarker for disease diagnosis and progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nContrasting with its evident oncogenic roles in various malignancies, a comprehensive study in pancreatic ductal adenocarcinoma patients found no pathogenic germline RABL3 variants, establishing an upper prevalence limit of less than 0.36%. This finding refines our understanding of RABL3’s impact in hereditary pancreatic cancer risk and guides future strategies for genetic testing."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sahar Nissim, Ignaty Leshchiner, Joseph D Mancias, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in RABL3 alter KRAS prenylation and are associated with hereditary pancreatic cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41588-019-0475-y"}], "href": "https://doi.org/10.1038/s41588-019-0475-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31406347"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31406347"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Weihua Zhang, Jian Sun, Junming Luo "}, {"type": "b", "children": [{"type": "t", "text": "High Expression of Rab-like 3 (Rabl3) is Associated with Poor Survival of Patients with Non-Small Cell Lung Cancer via Repression of MAPK8/9/10-Mediated Autophagy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Med Sci Monit (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.12659/msm.898632"}], "href": "https://doi.org/10.12659/msm.898632"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27164297"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27164297"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jun An, Zhiyong Liu, Qiong Liang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of Rabl3 and Cullin7 is associated with pathogenesis and poor prognosis in hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Pathol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.humpath.2017.07.008"}], "href": "https://doi.org/10.1016/j.humpath.2017.07.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28739496"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28739496"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yuhang Pan, Zhiyong Liu, Zhiying Feng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The overexpression of Rabl3 is associated with pathogenesis and clinicopathologic variables in hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Tumour Biol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1177/1010428317696230"}], "href": "https://doi.org/10.1177/1010428317696230"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28443498"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28443498"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Qi Li, Li Wang, Linge Zeng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Evaluation of the novel gene Rabl3 in the regulation of proliferation and motility in human cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Rep (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/or_00000876"}], "href": "https://doi.org/10.3892/or_00000876"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20596630"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20596630"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Zhiliang Xu, Huazhu Li, Chenyang Lin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Knockdown of RABL3 suppresses the proliferation and invasion of oral squamous cell carcinoma through inactivating the FAK/AKT pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Bioenerg Biomembr (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10863-021-09871-x"}], "href": "https://doi.org/10.1007/s10863-021-09871-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33438143"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33438143"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Yue Ma, Yanyi Ren, Huitao Wen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "circCOL1A1 Promotes the Progression of Gastric Cancer Cells through Sponging miR-145 to Enhance RABL3 Expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol Res (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2021/6724854"}], "href": "https://doi.org/10.1155/2021/6724854"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34631898"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34631898"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Muhammad Usman, Amber Ilyas, Zehra Hashim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of GIMAP7 and Rabl3 as Putative Biomarkers for Oral Squamous Cell Carcinoma Through Comparative Proteomic Approach."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pathol Oncol Res (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12253-019-00775-1"}], "href": "https://doi.org/10.1007/s12253-019-00775-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31748878"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31748878"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Nicholas J Roberts, Robert C Grant, Steven Gallinger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Germline sequence analysis of RABL3 in a large series of pancreatic ductal adenocarcinoma patients reveals no evidence of deleterious variants."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Chromosomes Cancer (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/gcc.22947"}], "href": "https://doi.org/10.1002/gcc.22947"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33724601"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33724601"}]}]}]}