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

Abstract

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.

LncRNA MEG3 suppresses migration and promotes apoptosis by sponging miR‐548d‐3p to modulate JAK–STAT pathway in oral squamous cell carcinoma

“…The subsequent western blot assay confirmed that miR‐548d‐3p intensified JAK–STAT pathway through suppressing expression of SOCS5 and SOCS6. In addition, our research indicated that miR‐548d‐3p accelerated the behaviors of OSCC cells via JAK–STAT pathway, which was recognized as one of the major oncogenic signaling pathways activated in a variety of human malignancies .…”

“…Given that SOCS5 and SOCS6 are known to be potential tumor suppressors , we reasoned that miR‐548d‐3p might play an important role on biological behaviors of OSCC cells by targeting SOCS5 and SOCS6. We structured the cells with overexpression of SOCS5 or SOCS6 effectively (Supporting Information Fig.…”

Pseudogene-Derived lncRNAs and Their miRNA Sponging Mechanism in Human Cancer

“…The tumor suppressive role of PTENP1 in esophageal squamous cell carcinoma was reported by Gong et al (2017). They found a downregulated expression of PTENP1 in esophageal squamous cell carcinoma compared with the corresponding adjacent normal tissues and overexpression of PTENP1 inhibited tumor proliferation (esophageal squamous cell carcinoma).…”

Retracted Article: Exosome-derived PTENP1 suppresses cisplatin resistance of bladder cancer (BC) by suppressing cell proliferation, migration and inducing apoptosis via the miR-103a/PDCD4 axis

“…27 In addition, enhanced expression of PTENP1 inhibited cell growth, migration in esophageal squamous cell carcinoma or breast cancer by regulating SOCS6 or miR-19b, respectively. 28,29 Therefore, it is imperative to disclose the role of PTENP1 in cisplatin resistance of BC cells. As bioinformatics analysis by online database MiRcode, PTENP1 could specically bind to miR-103a.…”