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STK31 regulates the proliferation and cell cycle of lung cancer cells via the Wnt/β‑catenin pathway and feedback regulation by c‑myc.

Oncology reports (2020-01-03)
Jie Xiong, Shigang Xing, Zheng Dong, Lei Niu, Qinghua Xu, Pingyi Liu, Peixia Yang
ABSTRACT

Lung cancer, which is a leading cause of cancer‑related deaths, is diagnosed at a male to female ratio of 2.1:1. Serine‑threonine kinase 31 (STK31) is a novel cancer/testis (CT)‑related gene that is highly expressed in several types of cancers, such as lung and colorectal cancer, and plays crucial roles in cancer. In the present study, increased expression of STK31 and β‑catenin was observed in lung cancer tissues and cell lines. Downregulation of STK31 expression in lung cancer cells significantly inhibited their proliferation by arresting the cell cycle in the G1 phase concurrent with decreased β‑catenin, c‑myc and cyclin D1 protein levels, while upregulation of STK31 had the opposite effects. In addition, STK31‑induced lung cancer cell viability, proliferation, cell cycle progression, and expression of related genes were completely attenuated by a Wnt/β‑catenin inhibitor (XAV939). Similar to XAV939, a c‑myc inhibitor (10058‑F4) also significantly attenuated STK31‑induced proliferation and cell cycle progression in lung cancer cells. Inhibiting c‑myc and TRRAP significantly decreased the expression of STK31, and a chromatin immunoprecipitation (ChIP) assay confirmed that c‑myc directly bound to the STK31 promoter. These results indicated that STK31 may act as an oncogene in lung cancer and that c‑myc may be the transcription factor that promotes STK31 expression. Moreover, the results suggested that c‑myc can also regulate STK31 expression in a positive feedback loop, and the downregulation of STK31 in lung cancer cells had an inhibitory effect on cell viability, cell proliferation and cell cycle progression, likely by inactivating the Wnt/β‑catenin pathway and positive feedback regulation by c‑myc.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
XAV939, ≥98% (HPLC)
Millipore
Immobilon-NC Transfer Membrane, 1 roll, 33 cm x 3 m, 0.45 µm pore size, Triton-free, mixed cellulose esters transfer membrane
Sigma-Aldrich
10058-F4, ≥98% (HPLC), solid