SMC1A is associated with radioresistance in prostate cancer and acts by regulating epithelial‐mesenchymal transition and cancer stem‐like properties

Abstract

Prostate cancer is one of the most commonly diagnosed cancers and a pressing health challenge in men worldwide. Radiation therapy (RT) is widely considered a standard therapy for advanced as well as localized prostate cancer. Although this primary therapy is associated with high cancer control rates, up to one‐third of patients undergoing radiation therapy becomes radio‐resistant and/or has tumor‐relapse/recurrence. Therefore, focus on new molecular targets and pathways is essential to develop novel radio‐sensitizing agents for the effective and safe treatment of prostate cancer. Here, we describe functional studies that were performed to investigate the role of structural maintenance of chromosome‐1 (SMC1A) in radioresistance of metastatic prostate cancer cells. Short hairpin RNA (shRNA) was used to suppress SMC1A in metastatic castration‐resistant prostate cancer cells, DU145 and PC3. Clonogenic survival assays, Western blot, RT‐PCR, and γ‐H2AX staining were used to assess the effect of SMC1A knockdown on radiation sensitivity of these prostate cancer cells. We demonstrate that SMC1A is overexpressed in human prostate tumors compared to the normal adjacent tissue. SMC1A knockdown limits the clonogenic potential, epithelial‐mesenchymal transition (EMT), and cancer stem‐like cell (CSC) properties of DU145 and PC3 cells and enhanced efficacy of RT in these cells. Targeted inhibition of SMC1A not only plays a critical role in overcoming radio‐resistance in prostate cancer cells, but also suppresses self‐renewal and the tumor‐propagating potential of x‐irradiated cancer cells. We propose that SMC1A could be a potential molecular target for the development of novel radio‐sensitizing therapeutic agents for management of radio‐resistant metastatic prostate cancer.

<p>Knockdown of lncRNA TUG1 Enhances Radiosensitivity of Prostate Cancer via the TUG1/miR-139-5p/SMC1A Axis</p>

“…33,34 Moreover, SMC1A knockdown regulated cell growth, colony formation and migration in PCa. 19,20 This study firstly verified the correlation among TUG1, miR-139-5p and SMC1A expression. SMC1A was a sponge gene of miR-139-5p, overexpression SMC1A could restore the effects of TUG1 knockdown on proliferation, apoptosis and radiosensitivity of PCa cells.…”

“…19 The recent reports indicated that SMC1A deletion enhanced the efficacy of radiotherapy by important regulation pathway through regulating the colony formation ability, the epithelial-mesenchymal transition (EMT), the cancer stem-like cell (CSC) population, DNA repair capacity and ROS. 20 In the current report, the target relationship among TUG1, miR-139-5p and SMC1A in PCa was verified. Our results revealed that TUG1 regulated SMC1A by sponging miR-139-5p, and SMC1A expression was positively correlated with TUG1.…”

“…A previous document revealed that SMC1A was associated with radioresistance in PCa by attenuating the NHEJ and HR pathways. 20 Further research is necessary to investigate whether there is a link between these two signal paths.…”

<p>Long Non-Coding RNA GAS5 Suppresses Tumor Progression and Enhances the Radiosensitivity of Prostate Cancer Through the miR-320a/RAB21 Axis</p>

“…27,28 However, searching molecular targets for elevating radiosensitivity becomes increasingly important to overcome the acquired radioresistance. 4,29 Fortunately in our study, lncRNA GAS5 was considered as a candidate biomarker for the radiation treatment of PCa.…”

“…2,3 The appearance of radioresistance severely limits the therapeutic efficacy of radiotherapy, having detrimental influence on the treatment and prognosis of PCa patients. 4 It is essential to enhance the radiosensitivity in PCa to develop the optional selective treatment of PCa.…”