Transfer RNA-derived RNA fragments (tRFs) belong to non-coding RNAs (ncRNAs) discovered in most carcinomas. Although some articles have demonstrated the characteristics of tRFs in gastric carcinoma (GC), the underlying mechanisms still need to be elucidated. Meanwhile, it was reported that the MAPK pathway was momentous in GC progression. Thus we focused on investigating whether tRF-Glu-TTC-027 could act as a key role in the progression of GC with the regulation of the MAPK pathway. We collected the data of the tRNA-derived fragments expression profile from six paired clinical GC tissues and corresponding adjacent normal samples in this study. Then we screened tRF-Glu-TTC-027 for analysis by using RT-PCR. We transfected GC cell lines with tRF-Glu-TTC-027 mimics or mimics control. Then the proliferation, migration, and invasion assays were performed to assess the influence of tRF-Glu-TTC-027 on GC cell lines. Fluorescence in situ hybridization assay was conducted to confirm the cell distribution of tRF-Glu-TTC-027. We confirmed the mechanism that tRF-Glu-TTC-027 influenced the MAPK signaling pathway and observed a strong downregulation of tRF-Glu-TTC-027 in clinical GC samples. Overexpression of tRF-Glu-TTC-027 suppressed the malignant activities of GC in vitro and in vivo. MAPK signaling pathway was confirmed to be a target pathway of tRF-Glu-TTC-027 in GC by western blot. This is the first study to show that tRF-Glu-TTC-027 was a new tumor-suppressor and could be a potential object for molecular targeted therapy in GC.
tRNA derivatives have been identified as a new kind of potential biomarker for cancer. Previous studies have identified that there were 30 differentially expressed tRNAs derivatives in breast cancer tissue with the high-throughput sequencing technique. This study aimed to investigate the possible biological function and mechanism of tRNA derivatives in breast cancer cells. One such tRF, a 5’-tRF fragment of tRF-17-79MP9PP (tRF-17) was screened in this study, which is processed from the mature tRNA-Val-AAC and tRNA-Val-CAC. tRF-17 with significantly low expression in breast cancer tissues and serum. The level of tRF-17 differentiated breast cancer from healthy controls with sensitivity of 70.4% and specificity of 68.4%. Overexpression of tRF-17 suppressed cells malignant activity. THBS1 (Thrombospondin-1) as a downstream target of tRF-17, and reduction of THBS1 expression also partially recovered the effects of tRF-17 inhibition on breast cancer cell viability, invasion and migration. Besides, THBS1, TGF-β1, Smad3, p-Smad3 and epithelial-to-mesenchymal transition related genes N-cadherin, MMP3, MMP9 were markedly down-regulated in tRF-17 overexpressing cells. Moreover, tRF-17 attenuated the THBS1-mediated TGF-β1/Smad3 signaling pathway in breast cancer cells. In general, the tRF-17/THBS1/TGF-β1/smad3 axis elucidates the molecular mechanism of breast cancer cells invasion and migration and could lead to a potential therapeutic target for breast cancer.
Purpose: Prior research has demonstrated that the postpartum period is associated with an increased risk of cognitive impairment. This study aims to investigate whether disrupted spontaneous neural activity exists in postpartum women without depression using resting-state functional magnetic resonance imaging (rs-fMRI) and to detect the relationship between these abnormalities and cognitive impairment.Materials and Methods: Postpartum women (n = 22) were compared with age- and education-matched nulliparous women (n = 23) using rs-fMRI. We calculated the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) values to evaluate spontaneous neural activity and detect the relationship between rs-fMRI data and cognitive performance.Results: Relative to nulliparous women, postpartum women had significantly decreased ALFF and ReHo values primarily in the left posterior cingulate cortex (PCC) and prefrontal cortex and increased ALFF values in left cerebellar posterior lobe. We found a positive correlation between the ALFF and ReHo values in the PCC and the complex figure test (CFT)-delayed scores in postpartum women (r = 0.693, p = 0.001; r = 0.569, p = 0.011, respectively). Moreover, the clock-drawing test (CDT) scores showed positive correlations with the ALFF and ReHo values in the right superior frontal gyrus (SFG; r = 0.492, p = 0.033; r = 0.517, p = 0.023, respectively).Conclusion: Our combined ALFF and ReHo analyses revealed decreased spontaneous neural activity, mainly in the PCC and prefrontal cortex, which was correlated with specific impaired cognitive functioning in postpartum women. This study may elucidate the neurophysiological mechanisms underlying postpartum cognitive impairment and enhance our understanding of the neurobiological aspects of the postpartum period.
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