It is known that the long noncoding RNAs (lncRNA) MALAT1 is associated with tumorigenesis and progression in various cancers; however, its functions and mechanisms in prostate cancer (PCa) initiation and progression are still unknown. In the present study, our findings revealed that MALAT1 plays a critical part in regulating PCa proliferation and glucose metabolism. Knockdown of MALAT1 affects the protein and mRNA levels of MYBL2. In addition, MALAT1 enhances the phosphorylation level of mTOR pathway by upregulating MYBL2. Knockdown of MALAT1 or MYBL2 in PCa cell lines significantly inhibits their proliferation capacity. Silencing MALAT1/MYBL2/mTOR axis in PCa cell lines affects their glycolysis and lactate levels, and we verified these findings in mice. Furthermore, we explored the underlying tumorigenesis functions of MYBL2 in PCa and found that high expression of MYBL2 was positively associated with TNM stage, Gleason score, PSA level, and poor survival rate in PCa patients. Taken together, our research suggests that MALAT1 controls cancer glucose metabolism and progression by upregulating MYBL2-mTOR axis.
With the discovery of new chemotherapeutic drugs, chemotherapy becomes increasingly valuable. However, the resistance of tumor cells to chemotherapeutic agents significantly limits the effectiveness and causes chemotherapy failure. MicroRNAs have been shown to regulate drug resistance in many types of cancer. In the present study, we measured the chemosensitivity of five bladder cancer (BCa) cell lines to seven commonly used chemotherapeutic drugs by Vita‑Blue assay. We then identified the most sensitive (5637) and most tolerant cell lines (H‑bc) and conducted a multi‑group test. This test included expression group analyses of coding and non‑coding genes (miR‑omic and RNA‑seq). Based on our analyses, we selected miR‑22‑3p as a target. We then determined its own target gene [neuroepithelial cell transforming 1 (NET1)] by bioinformatic analysis and confirmed this finding by TaqMan‑quantitative reverse transcription polymerase chain reaction (qRT‑PCR), western blot analysis and luciferase reporter assay. The effect of miR‑22‑3p on BCa multi‑chemoresistance was also determined by transfecting cells with the miR‑22‑3p‑mimic or miR‑22‑3p‑antagomiR. We assessed the involvement of NET1 in BCa chemoresistance by siRNA‑mediated NET1 inhibition or pINDUCER21‑enhanced green fluorescent protein‑NET1‑mediated overexpression. Plate colony formation and apoptosis assays were conducted to observe the effects of miR‑22‑3p and NET1 on BCa chemoresistance. In conclusion, our results suggest that miR‑22‑3p promotes BCa chemoresistance by targeting NET1 and may serve as a new prognostic biomarker for BCa patients.
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