Microphthalmia-associated transcription factor (MITF) is a basic helix-loop-helix leucine zipper transcription factor involved in the lineage-specific regulation of melanocytes, osteoclasts and mast cells. MITF is also involved in the progression of melanomas and other carcinomas, including the liver, pancreas and lung. However, the role of MITF in clear cell renal cell carcinoma (ccRCC) is largely unknown. This study investigates the functional role of MITF in cancer and the molecular mechanism underlying disease progression in ccRCC. MITF knockdown inhibited cell proliferation and shifted the cell cycle in ccRCC cells. In addition, MITF knockdown reduced wound healing, cell migration and invasion compared with the controls. Conversely, MITF overexpression in SN12C and SNU482 cells increased cell migration and invasion. Overexpression of MITF activated the RhoA/YAP signaling pathway, which regulates cell proliferation and invasion, and increased YAP signaling promoted cell cycle-related protein expression. Additionally, tumor formation was impaired by MITF knockdown and enhanced by MITF overexpression in vivo. In summary, MITF expression was associated with aggressive tumor behavior, and increased the migratory and invasive capabilities of ccRCC cells. These effects were reversed by MITF suppression. These results suggest that MITF is a potential therapeutic target for the treatment of ccRCC.

In bacteria, small non-coding RNAs (sRNAs) bind to target mRNAs and regulate their translation and/or stability. In the polycistronic galETKM operon of Escherichia coli, binding of the Spot 42 sRNA to the operon transcript leads to the generation of galET mRNA. The mechanism of this regulation has remained unclear. We show that sRNA-mRNA base pairing at the beginning of the galK gene leads to both transcription termination and transcript cleavage within galK, and generates galET mRNAs with two different 3’-OH ends. Transcription termination requires Rho, and transcript cleavage requires the endonuclease RNase E. The sRNA-mRNA base-paired segments required for generating the two galET species are different, indicating different sequence requirements for the two events. The use of two targets in an mRNA, each of which causes a different outcome, appears to be a novel mode of action for a sRNA. Considering the prevalence of potential sRNA targets at cistron junctions, the generation of new mRNA species by the mechanisms reported here might be a widespread mode of bacterial gene regulation.

Transcription of operons is initiated at the promoter of the first gene in the operon, continues through cistron junctions, and terminates at the end of the operon, generating a full-length mRNA. Here, we show that Rho-dependent termination of transcription occurs stochastically at a cistron junction, generating a stable mRNA that is shorter than the full-length mRNA.

Combination therapy with checkpoint inhibitors blocks inhibitory immune cell signaling and improves clinical responses to anticancer treatments. However, continued development of innovative and controllable delivery systems for immune-stimulating agents is necessary to optimize clinical responses. Herein, we engineered Salmonella to deliver recombinant granulocyte macrophage colony stimulating factor (GM-CSF) in a controllable manner for combination treatment with a programmed death-ligand 1 (PD-L1) inhibitor. The engineered Salmonella enabled delivery of recombinant GM-CSF into mouse tumors, activating recruitment of immune cells, such as M1-polarized macrophages, dendritic cells, and CD8⁺ T cells. Combination treatment with the PD-L1 inhibitor and engineered Salmonella increased the survival rate of tumor-bearing mice by 25%. New tumor growth was strongly suppressed, and visible tumors disappeared at 120 days post-infection (dpi) in mice rechallenged with additional tumor implantation at 100 dpi. The number of memory T cells increased >2-fold in tumor-rechallenged mice. Our findings demonstrate superiority of the engineered Salmonella as a cancer therapeutic agent with precise targeting ability, immune-boosting activity, and ease of combination with other therapeutics.

While autophagy degrades non-functional or unnecessary cellular components, producing materials for synthesizing cellular components, it can also provide energy for tumor development. Hederacolchiside A1 (HA1) derived from anemone raddeana has anticancer effects on several carcinomas by inducing apoptosis or exhibiting cytotoxicity, but the relationship with autophagy has not been studied. We investigated the association between HA1 and autophagy and evaluated its anticancer effect on colon cancer. HA1 induced accumulation of the autophagy-related markers LC3B and SQSTM1, with distinct vacuolar formation, unlike other autophagy inhibitors; the effects were similar to those of chloroquine. In addition, HA1 decreased the expression and proteolytic activity of lysosomal protein cathepsin C, reduced the growth of colon cancer cells in vitro, and inhibited tumor growth in vivo. It also reduced the expression of Ki-67 and cathepsin C in mouse tissues and reduced the growth of spheroids and organoids composed of cancer cells. Taken together, these results imply that HA1 regulates cell growth and autophagy and has potential as a promising therapeutic agent in colon cancer.

Current imaging techniques suffer from a lack of specificity and resolution, leading to inaccurate tumor imaging and limited applicability of targeted contrast agents, as they require cancer‐specific development. The need for enhanced contrast through improved tumor‐to‐background ratio (TBR) and the toxicity from repeated injections due to fading fluorescent signals further complicate the issue. Additionally, challenges in visualizing the entire 3D tumor with surface‐stained contrast agents highlight the demand for advanced imaging solutions for more precise surgical guidance. A novel approach is proposed utilizing Streptavidin Associated Salmonella (SAS) as a contrast agent for image‐guided surgeries. SAS selectively proliferates in cancerous tissues and secretes streptavidin upon induction, enabling the binding of subsequently injected biotin‐conjugated fluorescent dyes. This approach enhances tumor visualization with a TBR of up to 15.3, far surpassing conventional agents (TBR ∼ 2), while enabling prolonged 3‐day imaging, deep tumor penetration, and precise invasive margin delineation with a single contrast agent injection. Furthermore, biosafety evaluations confirmed efficient bacterial clearance, absence of systemic toxicity, and stable physiological responses, supporting its potential for safe clinical translation. This innovative method offers substantial improvements over existing fluorescent contrast agents and holds promise for both diagnostic and therapeutic applications in cancer surgery.