Background: Downregulated expression levels of microRNA-320a (miR-320a) were found in primary breast cancers and colorectal cancer. Previous findings indicated that miRNA-320a may involve in the cancer development. In this study, we explored the roles of miR-320a by targeting c-Myc in the tumor growth of hepatocellular carcinoma (HCC). Methods: Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was performed to detect the expression of miR-320a in 50 HCC tissues and four HCC cells. Luciferase reporter assay was conducted to confirm the direct downstream target of miR-320a in HEK-293 cells. The effect of miR-320a on endogenous c-Myc expression was investigated by transfecting miR-320a mimics into HepG2 and QGY-7703 cell lines. The c-Myc and miR-320a expressions were analyzed by immunohistochemistry (IHC) and qRT-PCR in the same HCC tissues. Furthermore, the biological functional correlation of miR-320a with c-Myc was determined by studying the effect of miR-320a mimics or c-Myc small interfering RNA (siRNA) on HCC cell proliferation and invasion.
Results: The expression of miR-320a was downregulated in 50 HCC tissues and 4 HCC cells. Luciferase assay revealed that c-Myc is a direct target of miR-320a. IHC and Western blot analysis showed that the c-Myc expression was inhibited by miR-320a in HCC tissues and cell lines. Upregulation of miR-320a suppressed the HCC cell proliferation and invasion capacity induced by inhibiting c-Myc, and the results were consistent with the effects of c-Myc siRNA on tumor suppression. These results revealed that miRNA-320a inhibits tumor proliferation and invasion by targeting c-Myc in HCC cells. Conclusion: Our results showed that miR-320a functions as a tumor suppressor in HCC. By targeting c-Myc directly, miR-320a inhibits the HCC cell growth. Our studies provide evidence of miR-320a as a potentially target for HCC treatment.

Reciprocal control of lncRNA-BCAT1 and -catenin pathway reveals lncRNA-BCAT1 long non-coding RNA acts as a tumor suppressor in colorectal cancer

Branching morphogenesis shapes the epithelial tissue architecture as proliferative branches navigate the extracellular matrix (ECM) microenvironment. In the mammary gland, pubertal terminal end buds (TEBs) drive stochastic ductal invasion to build a tree-like network. Although stem cell programs and hormonal regulation have been extensively characterized, the geometric principles underlying branch adaptation to ECM mechanics during morphogenesis remain incompletely defined. Here, using in vivo whole-mount imaging and ex vivo 3D organoid live imaging, we show that the mammary bifurcation angle occupies a characteristic range and, in organoids, that it oscillates dynamically during branch morphogenesis. We show that branch angles maintain a confined dynamic range with regular oscillations during both bud bifurcation and branch elongation, thereby supporting efficient branching morphogenesis. These angle dynamics are independent of major mammary-specific developmental growth and hormonal signaling, pointing to non-endocrine microenvironmental cues as potential regulators. Integrative analysis of branched epithelial RNA-seq and in vivo TEB microarray data further reveals the remodeling of cell adhesion pathways and epithelial–ECM interactions during network formation, with matrix metalloproteinase 14 (MMP14) specifically enriched in branched epithelia as a promising candidate mediator. Pharmacological inhibition of MMP14 disrupted branch angle oscillations and impaired organoid branching growth. Taken together, our findings, derived from murine tissue and organoid models, identify the homeostatic branch angle as a previously unrecognized biophysical signature of mammary branching that is maintained, in organoids, through MMP14-mediated ECM remodeling.