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PTEN pseudogene (PTENP1) has a tumor suppressive role in multiple cancers. However, its involvement in esophageal squamous cell carcinoma (ESCC) remains largely unknown. In this study, we set out to identify the role of PTENP1 in the development of ESCC. Gene Expression Omnibus database was employed to investigate the expression of PTENP1 in ESCC. sRNA target Database (StarBase v2.0) was used to query the downstream of PTENP1. Next, both in vitro and in vivo experiments were employed to explore the function. Cell proliferation was evaluated by CCK‐8, soft agar, and colony formation assays. Expression of relative genes was assessed by quantitative real‐time PCR (qRT‐PCR) and Western blotting. 3′UTR luciferase assay was used to confirm the miRNA binding. The clinical significance of PTENP1 was further validated by immunohistochemistry (IHC) and correlation with clinicopathological indicators in additional samples ( n  = 93). We found expression of PTENP1 in ESCC was lower than that in the corresponding adjacent normal tissues ( n  = 17). Overexpression of PTENP1 in Eca109 and TE‐1 cells resulted in inhibited proliferation and altered expression of SOCS6‐p‐STAT3‐HIF‐1α pathway both in vitro and in vivo. Subsequent IHC reported a similar trend in human ESCC samples. 3′UTR luciferase assay demonstrated that PTENP1 3′UTR decoyed miR‐17‐5p from binding to SOCS6. Moreover, PTENP1 expression was correlated with clinicopathological indicators to varying degrees, including histological grade, TNM stage, infiltration depth, lymph node metastasis, and overall survival. Taken together, these results suggested an anti‐oncogenic role of PTENP1. Meanwhile, PTENP1 may also serve as a candidate of prognostic indicator for ESCC patients.

PTENP1 inhibits the growth of esophageal squamous cell carcinoma by regulating SOCS6 expression and correlates with disease prognosis