Research Paper Volume 12, Issue 7 pp 6352—6369

FAM46C inhibits cell proliferation and cell cycle progression and promotes apoptosis through PTEN/AKT signaling pathway and is associated with chemosensitivity in prostate cancer

Libin Ma 1, *, , Huadong He 2, *, , Kang Jiang 2, , Peiwu Jiang 3, , Han He 2, , Shengjia Feng 4, , Kean Chen 5, , Jia Shao 2, , Gang Deng 2, ,

  • 1 Department of Nephrology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, Zhejiang, China
  • 2 Department of Urology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang, China
  • 3 Surgical Department I, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou 310007, Zhejiang, China
  • 4 Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang, China
  • 5 Department of Urology, The Second Hospital of Jiaxing, Jiaxing 314001, Zhejiang, China
* Equal contribution

received: September 27, 2019 ; accepted: February 23, 2020 ; published: April 13, 2020 ;

https://doi.org/10.18632/aging.103030
How to Cite

Copyright © 2020 Ma et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Family with sequence similarity 46 member C (FAM46C) is a non-canonical poly(A) polymerase that is associated with tumorigenesis. However, its role in prostate cancer development is not fully understood. Herein, we determined expression pattern of FAM46C in prostate cancer and further identified its effect on the tumorigenesis and chemosensitivity. FAM46C expression was decreased in prostate cancer tissues and cell lines compared with corresponding controls. FAM46C expression was significantly associated with the Gleason score, tumor size and overall survival. FAM46C knockdown in 22RV1 and DU145 cells significantly inhibited apoptosis and promoted cell proliferation and cell cycle progression as well as activation of AKT. FAM46C overexpression had an inverse effect in DU145 cells and inhibited tumor growth in vivo. FAM46C inhibited cell proliferation and cell cycle progression and induced apoptosis via the PTEN/AKT signaling pathway. FAM46C promoted PTEN expression through inhibiting PTEN ubiquitination. The prostate cancer cells and patient-derived xenograft (PDX) mice with high-FAM46C-expressing demonstrated an enhanced chemosensitivity to docetaxel. These findings suggest that FAM46C control cell proliferation, cell cycle and apoptosis through PTEN/AKT signaling pathway and is associated with chemosensitivity of prostate cancer. Modulation of their levels may offer a new approach for improving anti-tumor efficacy for chemotherapeutic agents in prostate cancer.

Abbreviations

FAM46C: Family with sequence similarity 46 member C; GSEA: Gene set enrichment analysis; HCC: hepatocellular carcinoma; TCGA: The Cancer Genome Atlas; HRP: Horseradish peroxidase; DAB: Diaminobenzidine; ATCC: American Tissue Culture Collection; CDS: Coding sequence; CCK-8: Cell Counting Kit-8; PI: Propidium iodide; qPCR: Quantitative real-time PCR; ECL: enhanced chemiluminescence; Co-IP: Co-immunoprecipitation; PDX: patient-derived xenograft; BLCA: bladder carcinoma; CESC: cervical cancer; COAD: colon and rectal adenocarcinoma; ESCA: esophageal cancer; HNSC: head and neck squamous cell carcinoma; KICH: kidney chromophobe; KIRC: kidney renal clear cell carcinoma; KIRP: kidney papillary cell carcinoma; LIHC: liver hepatocellular carcinoma; LUAD: lung adenocarcinoma; LUSC: lung squamous cell carcinoma; PCPG: pheochromocytoma and paraganglioma; PRAD: prostate adenocarcinoma; READ: rectum adenocarcinoma; SARC: sarcomas; SKCM: skin cutaneous melanoma; THCA: thyroid carcinoma; THYM: thymoma; STAD: stomach adenocarcinoma; CSCC: cervical squamous cell carcinoma; OC: ovarian cancer; PDAD: pancreatic ductal adenocarcinoma; UCEC: uterine corpus endometrial carcinoma.