By downregulating Ku80, hsa-miR-526b suppresses non-small cell lung cancer

Abstract

Ku80 is involved in DNA double-strand breaks (DSBs) repair. Ku80 is overexpressed in lung cancer tissues, yet, molecular mechanisms have not been examined. We identified that miRNA, hsa-miR-526b, is bound to the 3′-UTR of Ku80 mRNA, thus decreasing Ku80 expression in NSCLC cells. Hsa-miR-526b was downregulated in NSCLC tissues compared with corresponding non-tumorous tissues, and its expression was inversely correlated with Ku80 upregulation. Overexpression of Ku80 and downregulation of hsa-miR-526b were associated with poor clinical outcomes of NSCLC patients. Hsa-miR-526b suppressed NSCLC cell proliferation, clonogenicity, and induced cell cycle arrest and apoptosis. Hsa-miR-526b inhibited xenografts and orthotopic lung tumor growth. Further, Ku80 knockdown in NSCLC cells suppressed tumor properties in vitro and in vivo similar to hsa-miR-526b overexpression. In agreement, Ku80 restoration partially reversed cell cycle arrest and apoptosis induced by hsa-miR-526b in NSCLC cells in vitro and in vivo. In addition, hsa-miR-526b overexpression or Ku80 knockdown increased p53 and p21CIP1/WAF1 expression. These findings reveal that hsa-miR-526b is a potential target in cancer therapy.

Role of long non‐coding RNA in drug resistance in non‐small cell lung cancer

“…1 Lung cancer is traditionally classified as small cell lung cancer (SCLC) and non-small lung cancer (NSCLC). [2][3][4] NSCLC accounts for 85% of lung cancer cases. 5 NSCLC patient prognosis is poor as nearly half present with metastatic disease at diagnosis.…”

MicroRNAs, DNA Damage Response, and Cancer Treatment

“…Knockdown of miR-124 in rats has been proved that can protect against neuronal death and apoptosis by targeting Ku70 [67]. Furthermore, it has recently been shown that Ku80 is overexpressed in lung cancer and overexpressed hsa-miR-526b can downregulate the expression of Ku80, thus causing G0/G1 phase arrest and significantly suppressing the NSCLC growth in vitro and in vivo [68]. After the binding of the Ku70/Ku80 complex to the DSB, the catalytic subunit DNA-PKcs is recruited and activated.…”

Overexpression of miR‐623 suppresses progression of hepatocellular carcinoma via regulating the PI3K/Akt signaling pathway by targeting XRCC5

“…Further studies have shown that XRCC5 functions in the cellular process, primarily by maintaining telomeres, gene transcription, and the regulation of apoptosis and G2/M phase arrest. 21 Therefore, targeting XRCC5 might be a potential method to inhibit tumor growth. [17][18][19][20] Silencing the expression of XRCC5 could thus significantly inhibit tumor growth.…”

“…[17][18][19][20] Silencing the expression of XRCC5 could thus significantly inhibit tumor growth. 21 Therefore, targeting XRCC5 might be a potential method to inhibit tumor growth.…”