{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nmiR‐144 is emerging as a multifaceted regulator in several non‐malignant settings. In erythroid cells, elevated miR‐144 impairs the oxidative stress response by directly suppressing NRF2, thereby exacerbating anemia in sickle cell disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In the immune compartment, a miR‐144* isoform expressed by T cells attenuates anti–Mycobacterium tuberculosis responses by reducing TNF‐α and IFN‐γ production."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Circulating miRNAs including miR‐144 have been investigated as potential noninvasive biomarkers in type 2 diabetes"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "and also in studies examining ethnic‐specific miRNA patterns."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In airway epithelia, exposure to cigarette smoke up‐regulates miR‐144, which in turn suppresses CFTR protein expression, possibly contributing to chronic obstructive pulmonary disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Furthermore, miR‐144 is upregulated during human erythropoiesis where it targets RAB14 to promote red cell differentiation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", while its modulation of factors such as TIGAR has been implicated in the control of cell proliferation and apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Additional studies have revealed its participation in metabolic regulation in non‐alcoholic fatty liver disease"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ", in the host innate response against Mycobacterium tuberculosis via inhibition of antibacterial autophagy"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ", in placental trophoblast biology with reduced miR‐144 contributing to preeclampsia"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ", and in regulating osteoclastogenesis during bone remodeling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of cancer, miR‐144 displays complex and sometimes opposing functions that appear to be highly tissue‐ and context‐dependent. In colorectal cancer, lower miR‐144 levels contribute to enhanced mTOR signaling and increased tumor cell proliferation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": ", whereas in nasopharyngeal carcinoma its upregulation exerts oncogenic effects through PTEN suppression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": " In bladder cancer, miR‐144 is frequently downregulated and its restoration limits cell proliferation and invasive behavior via targeting EZH2"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "; similar tumor‐suppressive roles have been observed in thyroid cancer by repressing the E‐cadherin suppressors ZEB1/2."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": " In hepatocellular carcinoma, diminished miR‐144 levels facilitate proliferation and motility by releasing restraint on targets like E2F3"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": "and through ceRNA interactions with long noncoding RNAs."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": " Moreover, studies in epithelial cancers including renal cell carcinoma"}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "20", "end_ref": "22"}]}, {"type": "t", "text": "and clear cell variants"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "23"}]}, {"type": "t", "text": "as well as in breast cancer where miR‐144 overexpression is linked to radioresistance and altered epithelial‐to‐mesenchymal transition"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "24"}]}, {"type": "t", "text": "underscore its role as a modulator of oncogenic signaling. In gastric and esophageal carcinomas, miR‐144 impairs tumor aggressiveness by targeting factors such as PBX3"}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "25", "end_ref": "27"}]}, {"type": "t", "text": ", while similar suppressive actions have been documented in glioblastoma"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "28"}]}, {"type": "t", "text": ", non–small cell lung cancer"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "29"}]}, {"type": "t", "text": ", endometrial"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "30"}]}, {"type": "t", "text": ", cervical"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "31"}]}, {"type": "t", "text": ", and prostate cancers."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "32"}]}, {"type": "t", "text": " In addition, miR‐144 levels in clear cell renal carcinoma and its detection in exosomal cargo from mesenchymal stem cells further point to its significance in controlling cell cycle regulators and metastatic behavior."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "33", "end_ref": "35"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nEmerging mechanistic studies reveal that miR‐144 activity is tightly regulated by networks of noncoding RNAs that act as competing endogenous RNAs and influence its bioavailability. For instance, oncogenic long noncoding RNAs such as TUG1 and XIST sequester miR‐144, thereby derepressing downstream targets including EZH2, JAK2/STAT3, and cell cycle regulators."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "36"}, {"type": "fg_f", "ref": "29"}]}, {"type": "t", "text": " In endometrial cancer, NEAT1 similarly modulates the miR‐144/EZH2 axis to promote malignant phenotypes"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "30"}]}, {"type": "t", "text": ", while in epithelial malignancies, suppression of miR‐144 by PAX4 contributes to enhanced metastatic potential."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}]}, {"type": "t", "text": " Furthermore, mesenchymal stem cell–derived exosomal transfer of miR‐144 suggests a novel intercellular regulatory mechanism that may be exploited therapeutically."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "33"}, {"type": "fg_f", "ref": "31"}]}, {"type": "t", "text": " Collectively, these studies underscore the potential of targeting the miR‐144 regulatory network to modulate key signaling pathways involved in cell proliferation, apoptosis, migration, invasion, and therapy response across a spectrum of human diseases.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Carolyn Sangokoya, Marilyn J Telen, Jen-Tsan Chi "}, {"type": "b", "children": [{"type": "t", "text": "microRNA miR-144 modulates oxidative stress tolerance and associates with anemia severity in sickle cell disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2009-04-214817"}], "href": "https://doi.org/10.1182/blood-2009-04-214817"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20709907"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20709907"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yanhua Liu, Xinjing Wang, Jing Jiang, et al. 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