NEK6 Promotes the Progression of Osteosarcoma Through Activating STAT3 Signaling Pathway by Down-Regulation of miR-26a-5p

Abstract

Background Osteosarcoma is a malignant tumor originating from the skeletal system. There is no effective treatment other than surgery and chemotherapy, which seriously endangers the health of children and adolescents. NEK6 is a novel discovered Serine/Threonine protein kinase that can regulate cell cycle and activate several oncogenic pathways. Methods NEK6 expression in pan-cancer including sarcoma was evaluated using analysis tools of TIMER, UALCNA and GEPIA with TCGA database, and its association with overall survival in patients with sarcoma was also analyzed. TargetScan, tarbase, microT-CDS and Starbase online software were used to predict NEK6-targeted miRNAs, including miR-26a-5p. Tumor tissues from patients with osteosarcoma were collected for NEK6 and miRNA detection using RT-qPCR. NEK6 down-regulated by siRNAs or miR-26a-5p in osteosarcoma cells was detected by RT-qPCR, Western blot and Immunofluorescence staining assays. Effects of NEK6 knockdown on proliferation, migration, invasion and apoptosis of osteosarcoma cells were detected by CCK-8, wound healing, transwell and flow cytometry, respectively. The expressions of STAT3, metastasis and apoptosis-related genes were detected by Western blot. Results High expression of NEK6 and low expression of miR-26a-5p were lowly expressed in osteosarcoma and they were negative correlation. NEK6 has been confirmed as a direct target for miR-26a-5p. In addition, NEK6 down-regulated by siRNAs or miR-26a-5p led to inhibition of cell proliferation, migration and invasion while promoting cell apoptosis. The levels of phosphorylated STAT3 and metastasis genes (MMP-2, MMP-9) were inhibited, while apoptotic gene Bax was promoted and Bcl2 was inhibited by miR-26a-5p upregulation. Conclusion NEK6 can promote osteosarcoma progression via activating STAT3 signaling pathway, which is inhibited by miR-26a-5p, suggesting that NEK6 is a potential oncogene and miR-26a-5p is a suppressor of osteosarcoma. The strategy of inhibiting of NEK6 by miR-26a-5p may be an effective approach for osteosarcoma therapy.

PSMD14 is a novel prognostic marker and therapeutic target in osteosarcoma

“…Osteosarcomas are bone tumors that are commonly found in pediatric and adolescent patients; these tumors are characterized by a high risk of metastatic progression and recurrence after therapy [ 1 ]. Bone metastases are common, and in some cases, lung metastases also develop [ 10 ]. While research has focused on diagnosing and treating osteosarcoma, identifying prognostic indicators is also an important area of investigation.…”

Differential Expression of NEK Kinase Family Members in Esophageal Adenocarcinoma and Barrett’s Esophagus

“…Although they both can be phosphorylated by NEK9 [99], required for mitotic spindle formation [100], they display distinct expression [101], regulatory [102,103] patterns, and functions [21,104]. Overexpression of NEK6 has been reported in a variety of human cancers [105][106][107][108] and plays an oncogenic function. In our bioinformatics analyses, the overexpression of NEK6 in EAC was frequently detected in six of eight datasets, suggesting its important role in EAC.…”