Link Brain-Wide Projectome to Neuronal Dynamics in the Mouse Brain.

Knowledge about the neuronal dynamics and the projectome are both essential for understanding how the neuronal network functions in concert. However, it remains challenging to obtain the neural activity and the brain-wide projectome for the same neurons, especially for neurons in subcortical brain regions. Here, by combining in vivo microscopy and high-definition fluorescence micro-optical sectioning tomography, we have developed strategies for mapping the brain-wide projectome of functionally relevant neurons in the somatosensory cortex, the dorsal hippocampus, and the substantia nigra pars compacta. More importantly, we also developed a strategy to achieve acquiring the neural dynamic and brain-wide projectome of the molecularly defined neuronal subtype. The strategies developed in this study solved the essential problem of linking brain-wide projectome to neuronal dynamics for neurons in subcortical structures and provided valuable approaches for understanding how the brain is functionally organized via intricate connectivity patterns.

CircAPLP2 regulates the proliferation and metastasis of colorectal cancer by targeting miR-101-3p to activate the Notch signalling pathway.

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers, and it has a poor prognosis. Emerging evidence shows that circular RNAs (circRNAs) may act as good therapeutic targets for cancers due to their abundance and stability. However, their regulatory role in CRC needs further investigation. This study revealed that circAPLP2 was upregulated and miR-101-3p was downregulated in CRC tissues and cells compared to normal controls. Knockdown of circAPLP2 and overexpression of miR-101-3p inhibited the cell proliferation, migration and invasion and induced the apoptosis of CRC cells. circAPLP2 acted as a miR-101-3p sponge to upregulate its target gene Notch1, which activated cascades of proliferation- and metastasis-related proteins (c-Myc, cyclin D1, MMP-2 and MMP-9). Additionally, knockdown of circAPLP2 suppressed tumour growth and liver metastases of CRC in nude mice. Taken together, these results indicate that circAPLP2 promotes proliferation and metastasis by targeting miR-101-3p to activate the Notch signalling pathway in CRC, which provides new insights into the mechanisms underlying CRC malignancy and suggests a new therapeutic target.