HELQ suppresses migration and proliferation of non‐small cell lung cancer cells by repairing DNA damage and inducing necrosis

Abstract

HELQ plays a key role in DNA damage response and cell-cycle checkpoint regulation. It has been implicated in ovarian and pituitary tumors and may play a role in germ cell maintenance. This study investigated the role of HELQ in lung cancer. The expression of HELQ in patients with non-small-cell lung cancer (NSCLC) was downregulated compared with normal human lungs. Clinical prognostic analysis of Kaplan-Meier plots revealed that patients with NSCLC with low HELQ levels had a reduced overall survival. Further, we found that HELQ depletion enhanced lung cancer cell malignancy. Furthermore, overexpression of HELQ in lung cancer cells reduced cell migration in vitro, while DNA damage repair was inhibited. Both in vitro C Cell ell B Biology iology I International nternational ZHONG ET AL.

HELQ as a DNA helicase: Its novel role in normal cell function and tumorigenesis (Review)

“…Under normal conditions, HELQ is abundantly expressed in healthy human tissues, especially in the reproductive system, where it plays an important role in maintaining germ cell viability through RAD51 paralog-dependent repair. In addition, recent studies have reported that HELQ is abnormally expressed in various cancers (86)(87)(88)(89)(90). HELQ is important for cell proliferation, metastasis and chemotherapy resistance by regulating various molecular signaling pathways (for example, the NER, CHK1-RAD51 and ATM/ATR pathways).…”

“…Single-nucleotide polymorphism variants of HELQ have been associated with an increased risk of various cancers, including upper aerodigestive tract cancers (78,79), esophageal squamous cell carcinoma (80,81), head and neck cancers (82), gastric adenocarcinoma (81), and breast and ovarian cancer (OV) (83-85) through genome-wide association studies (Table III). Furthermore, there is accumulating evidence indicating that HELQ may act as a tumor suppressor for several cancers, such as osteosarcoma (86), OV (12,13,34,77,87), chronic lymphocytic leukemia (CLL) (88), non-small cell lung cancer (NSCLC) (89) and endometrial stromal sarcoma (ESS) (Table IV) (90). HELQ is an important regulator of cancer proliferation, invasion, migration and can contribute to poor patient prognosis and platinum resistance through several mechanisms (13,86,87) in different types of tumors (Fig.…”

“…HELQ is downregulated in NSCLC tissues and cells, while the malignancy of lung cancer cells was enhanced by HELQ depletion. HELQ overexpression inhibits cell proliferation and migration by suppressing DNA damage repair, and promotes cell death by inducing necrosis through its interaction with receptor-interacting serine/threonine kinase 3 (RIPK3) (89). HELQ is a favorable prognostic factor for patients with NSCLC, and low HELQ levels in patients with NSCLC were associated with a reduced overall survival (OS) through a Kaplan-Meier plotter.…”