HELQ reverses the malignant phenotype of osteosarcoma cells via CHK1-RAD51 signaling pathway

Abstract

HELQ is a DNA helicase important for repair of DNA lesions and has been linked to several types of cancer. However, little is known about its relationship with osteosarcoma (OS) and its mechanism. In the present study, the expression of HELQ and its downstream mediators in OS cells was assayed by quantitative PCR and western blot analysis. The function of HELQ in OS cells was investigated by Transwell invasion, wound healing, CCK8 assays and Comet assay. The results demonstrated that HELQ gene and protein were expressed in OS cells. OS cell invasion, migration, proliferation and DNA damage repair were enhanced by HELQ knock-down with shRNA-lentivirus and inhibited by HELQ overexpression with lentivirus transfection. Furthermore, the antitumor activities of HELQ may be associated with upregulated expression of the DNA damage-related proteins CHK1 and RAD51. Our findings indicated that HELQ confers an anti-invasive phenotype on OS cells by activating the CHK1-RAD51 signaling pathway and suggested that HELQ could be recognized as a promising therapeutic target for OS and other types of malignant tumors.

Deep RNA sequencing reveals the dynamic regulation of miRNA, lncRNAs, and mRNAs in osteosarcoma tumorigenesis and pulmonary metastasis

“…Five significant miRNAs, miR-520c-3p (degree = 115), miR-30a-5p (degree = 111), miR-520b (degree = 111), miR-940 (degree = 101), and miR-548j-5p (degree = 95) had the most target genes. Significantly, there were 16 miRNA–mRNA pairs which may play crucial roles in OS tumorigenesis, such as miR-133a-3p and its target genes SERPINH1 34 , TPM4 35 , MRC2 36 , STK17B 37 , CD33 38 and PIK3CG 39 , miR-378a-5p and RAD51 40 , miR-378b and target genes UHRF1 41 and SRC 42 , miR-378c and PIK3CG 39 , UHRF1 41 and SRC 42 , miR-378f and UHRF1 41 , miR-378g and NOTCH2 43 , miR-378h and UHRF1 41 , and miR-449a and SATB1 44 .…”

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

“…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.…”

Rad51 filament dynamics and its antagonistic modulators

“…The human homologue HELQ (helicase POLQ-like) acts in a 3' to 5' direction and interacts with Rad51 paralogs [135], consistent with its proposed roles in disassembling Rad51 from duplex DNA although there is a lack of direct proof in human cells. Functionally, HELQ has been linked to chemoresistance in epithelial ovarian cancer, as well as reversing the malignant phenotype of osteosarcoma cells via the CHK1-Rad51 pathway [136]. Furthermore, deletion of the C-terminus of HELQ in mouse haematopoietic stem cells and human (U2OS) cells results in reduction in cell viability and HR efficiency, as well as increased tumour growth in mice [137].…”