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Colon cancer is a major malignant neoplasm with a low survival rate for late-stage patients. Therefore, the investigation of molecules regulating colon cancer progression and the discovery of novel therapeutic targets is critical. Mitochondria play a vital role in maintaining the homeostasis of cells. Abnormal mitochondrial metabolism alterations and the induction of glycolysis can facilitate tumor growth; therefore, targeting mitochondrial molecules is suggested to be a promising strategy for cancer treatment. In this study, we investigated the role of this largely unknown mitochondrial factor, chromosome 20 open reading frame 7 (C20orf7), in colon cancer progression. Clustered regularly interspaced short palindromic repeats (CRISPR) technology was utilized for C20orf7 depletion, and functional assays were performed to examine the regulation of C20orf7 in colon cancer cells. We demonstrated that C20orf7 facilitates epithelial–mesenchymal transition (EMT)-mediated cell migration and promotes the proliferation of colon cancer. The anti-cancer drug 5-fluorouracil (5FU) was also applied, and C20orf7 was targeted with a combination of 5FU treatment, which could further enhance the anti-cancer effect in the colon cancer cell line and the xenograft mice model. In summary, this study demonstrated, for the first time, that C20orf7 plays a promotional role in cancer tumorigenesis and could be a promising therapeutic target in colon cancer treatment.

Scientists have studied intensively the gene delivery carriers for treating genetic diseases. However, there are challenges that impede the application of naked gene-based therapy at the clinical level, such as quick elimination of the circulation, lack of membrane penetrability, and poor endosome trapping. Herein, we develop graphene quantum dots (GQDs)-derivative nanocarriers and introduce polyethylenimine (PEI) to equip the system with enhanced biocompatibility and abundant functional groups for modification. In addition to carrying green fluorescent protein (GFP) as an example of gene delivery, this system covalently binds colon cancer cells targeted antibody and epidermal growth factor receptor (EGFR) to enhance cell membrane penetrability and cell uptake of nanocarriers. To achieve multistrategy cancer therapy, the anticancer drug doxorubicin (Dox) is noncovalently encapsulated to achieve pH-induced drug release at tumor sites and leaves space for further functional gene modification. This nanoparticle serves as a multifunctional gene delivery system, which facilitates improved cytotoxicity and longer-sustained inhibition capacity compared to free Dox treatments in colon cancer cells. Moreover, our GQD composites display compatible tumor suppression ability compared with the free Dox treatment group in xenograft mice experiment with significantly less toxicity. This GQD nanoplatform was demonstrated as a multifunctional gene delivery system that could contribute to treating other genetic diseases in the future.

Simple Summary Glioblastoma multiforme is a common and lethal malignant brain tumor, and occurrence of therapeutic resistance in GBM often causes relapse. Therefore, this study aimed to find a new therapeutic strategy to treat these malignant tumors. In the current study, combined abemaciclib with an autophagy inhibitor, MPT0L145, significantly reduced cell proliferation and elevated intracellular reactive oxygen species (ROS) level. A blood–brain barrier permeability assay also showed that MPT0L145 could penetrate endothelial cells and has a penetration ability similar to that of TMZ. Therefore, this work represents a potential therapeutic strategy for treating the GBM in the future. Abstract Glioblastoma multiforme (GBM) is the most malignant brain tumor in the world, only 25% of GBM patients were alive one year after diagnosis. Although Temozolamide combined with radiation therapy more effectively prolonged the survival rate than radiation alone, the overall survival rate is still dismal. Therefore, a new therapeutic strategy is urgently needed. CDK4/6 inhibitors are newly FDA-approved agents to treat HR-positive, HER2-negative advanced, and metastatic breast cancers, and preclinical results showed that CDK4/6 inhibitors significantly reduced cell proliferation and tumor growth. However, several studies have suggested that CDK4/6 inhibitor-induced non-genetic changes caused treatment failure, including autophagy activation. Therefore, this study aimed to combine an autophagy inhibitor, MPT0L145, with abemaciclib to improve therapeutic efficiency. The use of abemaciclib effectively inhibited cell proliferation via suppression of RB phosphorylation and induced autophagy activation in GBM cancer cells. MPT0L145 treatment alone not only blocked autophagy activation, but also induced generation of ROS and DNA damage in a concentration-dependent manner. Importantly, MPT0L145 had a comparable penetration ability to TMZ in our blood brain barrier permeability assay. Combined MPT0L145 with abemaciclib significantly reduced cell proliferation, suppressed RB phosphorylation, and increased ROS production. In conclusion, the data suggested that blocking autophagy by MPT0L145 synergistically sensitized GBM cancer cells to abemaciclib and represents a potential therapeutic strategy for treating GBM in the future.

There has been great improvement in nanomaterial fields, and the biomedical potential of nanomaterials as drug delivery system is under intensive studies. Among them, graphene quantum dots (GQDs) are considered to be the next generation of carbon-based nanomaterial for biomedical applications. In this study, we utilized green fluorescent protein (GFP) nucleic acid, DNA-targeting chemoreagent doxorubicin (DOX), and branched polyethyleneimine (PEI) conjugated GQDs, to form pH-responsive nanostar drug carrier for colon cancer suppression investigation. GFP expression plasmid was applied to examine the delivery capacity of our drug carrier. DOX was encapsulated by intrinsic π-π interaction to form GQDs-polymer-DOX conjugates (GECD) as drug carrier. We proposed that once GECD enters the tumor lesion, the acidic tumor microenvironment protonated the tertiary amine of GECD from neutral to mild positive, possessed higher affinity to negatively charged cell membrane, triggered the drug release, and then cancer cells would be inhibited. The anti-cancer ability of our drug carrier system, GECD, was demonstrated in cancer cells by cell proliferation assay. Moreover, GECD exhibited its powerful anti-tumor capacity in the mice xenograft model. The in vivo and in vitro results indicate that our GECD with high cancer suppression capacity could be adopted for future cancer therapy.