Background:Growing evidence suggests that miR-29a has an important role in regulating tumourigenesis and development of various types of cancer. However, the role and the underlying mechanism of miR-29a in colorectal cancer (CRC) remain largely unknown.Methods:MiR-29a targeted gene was identified by the luciferase assay and western blot. MiR-29a function was analysed by invasion assays and the orthotopic transplantation mouse model. The miR-29a pathway was assayed by real-time PCR, western blot and chip analysis.Results:KLF4 was identified as a direct target gene of miR-29a. MiR-29a promoted CRC cell invasion, which was blocked by re-expression of KLF4. In addition, MMP2 was identified as a novel direct target of KLF4. Both miR-29a overexpression and KLF4 knockdown promoted MMP2 expression but inhibited E-cadherin expression. Furthermore, clinical data indicated that both miR-29a high expression and KLF4 mRNA low expression were associated with metastasis and poor prognosis in CRC patients, and KLF4 protein expression was inversely correlated with MMP2 but positively correlated with E-cad protein expression.Conclusion:Increased expression of miR-29a promoted CRC metastasis by regulating MMP2/E-cad through direct targeting KLF4, which highlights the potential of the miR-29a inhibitor as a novel agent against CRC metastasis.

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The radioresistance induced by hypoxia is the major obstacle in the successful treatment of cancer radiotherapy. p21 was initially identified as a widespread inhibitor of cyclin-dependent kinases, through which mediates the p53-dependent cell cycle G1 phase arrest in response to a variety of stress stimuli. In this study, we discovered a novel function of p21, which participated in the regulation of metabolic pathways under hypoxia. We found that p21 was upregulated in glioblastoma (GBM) cells under hypoxic conditions, which enhanced the radioresistance of GBM cells. In principle, HIF-1α is bound directly to the hypoxia response elements (HREs) of the p21 promoter to enhance its transcription activity, in turn, p21 also promoted the transcription of HIF-1α at the mRNA level and maintained HIF-1α function under oxygen deficiency. The positive correlation between p21 and HIF-1α augmented Glut1/LDHA-mediated glycolysis and aggravated the radioresistance of GBM cells. Thus, our results constructed a positive feedback circuit comprising p21/HIF-1α that might play a key role in enhancing the radioresistance of GBM under hypoxia.

Supplementing bronchoscopic forceps biopsy with brushing improves diagnostic yield in lung cancer. In cases of endobronchial exophytic tumors, pre-biopsy brushing appears to be superior to post-biopsy brushing.