MicroRNA-106b-5p regulates cisplatin chemosensitivity by targeting polycystic kidney disease-2 in non-small-cell lung cancer

Abstract

Systemic therapy with cytotoxic agents remains one of the main treatment methods for non-small-cell lung cancer (NSCLC). Cisplatin is a commonly used chemotherapeutic agent, that, when combined with other drugs, is an effective treatment for NSCLC. However, effective cancer therapy is hindered by a patient's resistance to cisplatin. Unfortunately, the potential mechanism underlying such resistance remains unclear. In this study, we explored the mechanism of microRNA-106b-5p (miR-106b-5p), which is involved in the resistance to cisplatin in the A549 cell line of NSCLC. Quantitative real-time PCR was used to test the expression of miR-106-5p in the A549 and the A549/DDP cell line of NSCLC. The cell counting kit-8 assay was used to detect cell viability. Flow cytometry was used to measure cell cycle and cell apoptosis. Luciferase reporter assays and western blot were performed to confirm whether polycystic kidney disease-2 (PKD2) is a direct target gene of miR-106b-5p. Immunohistochemistry was performed to examine the distribution of PKD2 expression in patients who are sensitive and resistant to cisplatin. The experiments indicated that the expression of miR-106b-5p was significantly decreased in A549/DDP compared with that in A549. MiR-106b-5p affected the tolerance of cells to cisplatin by negatively regulating PKD2. Upregulation of miR-106b-5p or downregulation of PKD2 expression can cause A549/DDP cells to become considerably more sensitive to cisplatin. The results showed that miR-106b-5p enhanced the sensitivity of A549/DDP cells to cisplatin by targeting the expression of PKD2. These findings suggest that the use of miR-106b-5p may be a promising clinical strategy in the treatment of NSCLC.

miR‐106b‐5p promotes aggressive progression of hepatocellular carcinoma via targeting RUNX3

“…Recent studies have revealed that miR‐106b‐5p may play an oncogenic role in various cancer types by promoting malignant cell viability and invasion . For example, Lu et al revealed that miR‐106b‐5p could mediate the constitutive activation of Wnt/β‐catenin signaling, and promote renal cell carcinoma aggressiveness and stem cell‐like phenotypes; Wei et al indicated that miR‐106b‐5p overexpression promoted proliferation and inhibited apoptosis by downregulating BTG3 expression in vitro, as well as xenograft tumor formation in vivo; Liu et al found that miR‐106b‐5p could boost glioma tumorigensis by targeting multiple tumor suppressor genes, including RBL1, RBL2, and CASP8; Yu et al demonstrated that miR‐106b‐5p enhanced the sensitivity of nonsmall‐cell lung cancer cell line A549/DDP to cisplatin by targeting the expression of PKD2. Consistent to these previous studies, our data here confirmed the upregulation of miR‐106b‐5p in HCC tissues compared with noncancerous adjacent liver tissues, and also demonstrated the significant associations of miR‐106b‐5p overexpression with advanced TNM stage, as well as short recurrence‐free and overall survivals.…”

“…Recent studies have revealed that miR-106b-5p may play an oncogenic role in various cancer types by promoting malignant cell viability and invasion. [14][15][16][17][18][19][20] For example, Lu et al 14 revealed that miR-106b-5p could mediate the constitutive activation of Wnt/β-catenin signaling, and promote renal cell carcinoma aggressiveness and stem cell-like phenotypes; Wei et al 15 indicated that miR-106b-5p overexpression promoted proliferation and inhibited apoptosis by downregulating BTG3 F I G U R E 7 RUNX3 over-expression reverses the oncogenic effects of miR-106b-5p in SMMC7721 cell line. A, Western blot analysis confirmed that the downregulation of RUNX3 protein expression caused by the upregulation of miR-106b-5p was recovered by the co-transfection with RUNX3-vector in HSMMC7721 cells (**P < .01).…”

“…It belongs to the miR‐106b seed family which has been indicated to be closely associated with cell proliferation, cell cycle, and cell motility . Accumulating studies have reported that miR‐106b‐5p plays an important role in various cancers through diverse mechanisms . Particularly, Shi et al found that the expression of miR‐106b‐5p was higher in HCC tissues and cell lines than that in nontumor tissues and hepatocytes, respectively.…”

“…13 Accumulating studies have reported that miR-106b-5p plays an important role in various cancers through diverse mechanisms. [14][15][16][17][18][19][20] Particularly, Shi et al 21 found that the expression of miR-106b-5p was higher in HCC tissues and cell lines than that in nontumor tissues and hepatocytes, respectively. The authors also indicated that miR-106b-5p upregulation promoted stem cell-like properties of HCC cells by targeting PTEN via PI3K/Akt pathway.…”

<p>miR-106b promotes proliferation and invasion by targeting Capicua through MAPK signaling in renal carcinoma cancer</p>

“…Yu et al, found miR-106b enhanced the sensitivity of A549/DDP cells to cisplatin by targeting the expression of PKD2. 13 Yao et al, have indicated overexpression of miR-106b shortened the G0/G1 phase and accelerated cell migration and invasion of gastric cancer cells. 14 Liu et al, demonstrated that miR-106b negatively regulated osteogenic differentiation of mesenchymal stem cells in vitro.…”