{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPTENP1, a long non‐coding pseudogene of the tumor suppressor PTEN, has emerged as a critical regulator of oncogenic signaling through its function as a competing endogenous RNA (ceRNA). By “sponging” multiple microRNAs—including miR‐17, miR‐19, miR‐20a, miR‐21, miR‐27a‐3p, miR‐106b, and others—PTENP1 relieves PTEN transcripts from microRNA-mediated repression. This sequestration promotes PTEN expression and, consequently, suppresses key proliferative and survival pathways such as PI3K/AKT. Studies in hepatocellular carcinoma, clear‐cell renal cell carcinoma, oral and head and neck squamous cell carcinomas, as well as in certain breast cancer models, have demonstrated that PTENP1 restoration leads to reduced cell proliferation, migration, invasion, and tumor growth."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nClinically, aberrant regulation of PTENP1—often via promoter hypermethylation or transcriptional downregulation—has been associated with more aggressive tumor phenotypes and poorer outcomes in diverse settings such as endometrial and gastric cancers. Reduced PTENP1 expression correlates with larger tumor size, deeper invasion, lymphatic metastasis, and chemoresistance, while restoration of its expression (or its presence in exosomal cargo) emerges as a promising diagnostic and prognostic biomarker. Furthermore, genetic variations within PTENP1, including polymorphisms that alter its transcript level and miRNA binding affinity, have been linked to differences in cancer susceptibility, as well as to risks for oral squamous cell carcinoma and bladder cancer."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "19"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its ceRNA‐mediated modulation of PTEN, additional studies have highlighted the nuanced, context‐dependent effects of PTENP1 on therapeutic response and cellular behavior. In certain breast cancer models, for example, modulation of PTENP1 and its interplay with microRNAs—such as via alterations in 3′UTR dynamics—affects cell survival and sensitivity to chemotherapy. Replication studies have further confirmed that altering PTENP1 levels impacts PTEN protein abundance and tumor cell proliferation, while genetic polymorphisms in PTENP1 are associated with cognitive outcomes in glioma patients. Collectively, these findings underscore the multifaceted roles of PTENP1 in tumor biology and illustrate its promise as both a biomarker and a therapeutic target."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "20", "end_ref": "25"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Gan Yu, Weimin Yao, Kiranmai Gumireddy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pseudogene PTENP1 functions as a competing endogenous RNA to suppress clear-cell renal cell carcinoma progression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer Ther (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1535-7163.MCT-14-0245"}], "href": "https://doi.org/10.1158/1535-7163.MCT-14-0245"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25249556"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25249556"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Chiu-Ling Chen, Yen-Wen Tseng, Jaw-Ching Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Suppression of hepatocellular carcinoma by baculovirus-mediated expression of long non-coding RNA PTENP1 and MicroRNA regulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomaterials (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biomaterials.2014.12.023"}], "href": "https://doi.org/10.1016/j.biomaterials.2014.12.023"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25617127"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25617127"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ling Gao, Wenhao Ren, Linmei Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PTENp1, a natural sponge of miR-21, mediates PTEN expression to inhibit the proliferation of oral squamous cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Carcinog (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/mc.22594"}], "href": "https://doi.org/10.1002/mc.22594"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27862321"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27862321"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jiannan Liu, Yue Xing, Liqun Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Decreased expression of pseudogene PTENP1 promotes malignant behaviours and is associated with the poor survival of patients with HNSCC."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep41179"}], "href": "https://doi.org/10.1038/srep41179"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28112249"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28112249"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Rupeng Zhang, Yuenan Guo, Zhenchi Ma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long non-coding RNA PTENP1 functions as a ceRNA to modulate PTEN level by decoying miR-106b and miR-93 in gastric cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.15317"}], "href": "https://doi.org/10.18632/oncotarget.15317"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28212532"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28212532"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "R-K Li, J- Gao, L-H Guo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PTENP1 acts as a ceRNA to regulate PTEN by sponging miR-19b and explores the biological role of PTENP1 in breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Gene Ther (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cgt.2017.29"}], "href": "https://doi.org/10.1038/cgt.2017.29"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28731027"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28731027"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Tongyu C Wikramanayake, Penelope Hirt, Maram Almastadi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Increased IL-17-expressing γδ T cells in seborrhoeic dermatitis-like lesions of the Mpzl3 knockout mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Dermatol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/exd.13798"}], "href": "https://doi.org/10.1111/exd.13798"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30307058"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30307058"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Xue Gao, Tao Qin, Jun Mao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PTENP1/miR-20a/PTEN axis contributes to breast cancer progression by regulating PTEN via PI3K/AKT pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Clin Cancer Res (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13046-019-1260-6"}], "href": "https://doi.org/10.1186/s13046-019-1260-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31196157"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31196157"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Yanxian Lai, Jianyong Li, Lintao Zhong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The pseudogene PTENP1 regulates smooth muscle cells as a competing endogenous RNA."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Sci (Lond) (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/CS20190156"}], "href": "https://doi.org/10.1042/CS20190156"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31235554"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31235554"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Zhan Wang, Yuxin Song, Xingwen Han, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long noncoding RNA PTENP1 affects the recovery of spinal cord injury by regulating the expression of miR-19b and miR-21."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Physiol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcp.29253"}], "href": "https://doi.org/10.1002/jcp.29253"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31583718"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31583718"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "L Ou, T-Y Xiang, X-Y Hao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Reduced long non-coding RNA PTENP1 contributed to proliferation and invasion via miR-19b/MTUS1 axis in patients with cervical cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur Rev Med Pharmacol Sci (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.26355/eurrev_202004_20993"}], "href": "https://doi.org/10.26355/eurrev_202004_20993"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32373949"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32373949"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "T F Kovalenko, A V Sorokina, L A Ozolinia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "[Pseudogene PTENP1 5'-region methylation in endometrial cancer and hyperplasias]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bioorg Khim (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1134/s1068162013040109"}], "href": "https://doi.org/10.1134/s1068162013040109"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24707726"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24707726"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Lei Dong, Peng Qi, Mi-Die Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Circulating CUDR, LSINCT-5 and PTENP1 long noncoding RNAs in sera distinguish patients with gastric cancer from healthy controls."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Cancer (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ijc.29484"}], "href": "https://doi.org/10.1002/ijc.29484"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25694351"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25694351"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Yugang Ge, Yu He, Mingkun Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Polymorphisms in lncRNA PTENP1 and the Risk of Gastric Cancer in a Chinese Population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dis Markers (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2017/6807452"}], "href": "https://doi.org/10.1155/2017/6807452"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28931965"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28931965"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "C Xin, J-L Li, Y-X Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Polymorphisms in lncRNA PTENP1 and the risk of oral squamous cell carcinoma in a Chinese population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur Rev Med Pharmacol Sci (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.26355/eurrev_201809_15822"}], "href": "https://doi.org/10.26355/eurrev_201809_15822"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30229832"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30229832"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Rui Zheng, Mulong Du, Xiaowei Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exosome-transmitted long non-coding RNA PTENP1 suppresses bladder cancer progression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12943-018-0880-3"}], "href": "https://doi.org/10.1186/s12943-018-0880-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30285771"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30285771"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Ruichao Chen, Minfen Zhang, Wenya Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Estrogen affects the negative feedback loop of PTENP1-miR200c to inhibit PTEN expression in the development of endometrioid endometrial carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-018-1207-4"}], "href": "https://doi.org/10.1038/s41419-018-1207-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30584245"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30584245"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Chengping Wu, Fang Wang, Li Tan "}, {"type": "b", "children": [{"type": "t", "text": "Role and the molecular mechanism of lncRNA PTENP1 in regulating the proliferation and invasion of cervical cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene Ther (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41434-020-00189-8"}], "href": "https://doi.org/10.1038/s41434-020-00189-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32973352"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32973352"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Carina Nicu, Tongyu C Wikramanayake, Ralf Paus "}, {"type": "b", "children": [{"type": "t", "text": "Clues that mitochondria are involved in the hair cycle clock: MPZL3 regulates entry into and progression of murine hair follicle cycling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Dermatol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/exd.14213"}], "href": "https://doi.org/10.1111/exd.14213"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33040410"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33040410"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Synnøve Yndestad, Eilin Austreid, Kai Ove Skaftnesmo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Divergent Activity of the Pseudogene "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "PTENP1"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " in ER-Positive and Negative Breast Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer Res (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1541-7786.MCR-17-0207"}], "href": "https://doi.org/10.1158/1541-7786.MCR-17-0207"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29021233"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29021233"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Xianbiao Shi, Xiaoqiao Tang, Lei Su "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of Long Noncoding RNA PTENP1 Inhibits Cell Proliferation and Migration via Suppression of miR-19b in Breast Cancer Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Res (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3727/096504017X15123838050075"}], "href": "https://doi.org/10.3727/096504017X15123838050075"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29212574"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29212574"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Yehua Zhang, Changqing Xu "}, {"type": "b", "children": [{"type": "t", "text": "G allele of rs7853346 polymorphism in PTENP1 enhances the proliferation of multiple myeloma cancer stem cells by promoting the expression of PTENP1 and its downstream signaling molecules."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biochem (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcb.29280"}], "href": "https://doi.org/10.1002/jcb.29280"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31338886"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31338886"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "John Kerwin, Israr Khan "}, {"type": "b", "children": [{"type": "t", "text": "Replication Study: A coding-independent function of gene and pseudogene mRNAs regulates tumour biology."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.51019"}], "href": "https://doi.org/10.7554/eLife.51019"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32314732"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32314732"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Glena Travis, Nahal Haddadi, Ann M Simpson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Studying the Oncosuppressive Functions of PTENP1 as a ceRNA."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Methods Mol Biol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/978-1-0716-1503-4_11"}], "href": "https://doi.org/10.1007/978-1-0716-1503-4_11"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34165715"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34165715"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Sen Yang, Zhan-Zhao Fu, Yan-Qiu Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rs7853346 Polymorphism in lncRNA-PTENP1 and rs1799864 Polymorphism in CCR2 are Associated with Radiotherapy-Induced Cognitive Impairment in Subjects with Glioma Via Regulating PTENP1/miR-19b/CCR2 Signaling Pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Genet (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10528-021-10145-9"}], "href": "https://doi.org/10.1007/s10528-021-10145-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34799795"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34799795"}]}]}]}