Jingyi Huang

In most solid tumors, cellular energy metabolism is primarily dominated by aerobic glycolysis, which fulfills the high demand for biomacromolecules at the expense of reduced ATP production efficiency. Elucidation of the mechanisms by which rapidly proliferating malignant cells acquire sufficient energy in this state of inefficient ATP production from glycolysis could enable the development of metabolism-targeted therapeutic strategies. In this study, we observed a significant association between elevated expression levels of the long noncoding RNA small nuclear RNA host gene 17 (SNHG17) and unfavorable prognosis in breast cancer. SNHG17 promoted breast cancer cell proliferation by augmenting mitochondrial ATP production. Mechanistically, SNHG17 directly interacted with the P65 subunit of NF-κB and phosphorylated P65 at the threonine 505 site. SNHG17 bound to P65 at its truncated loop2 site, recruited P65 to mitochondria, and coregulated the transcriptional activation of mitochondrial DNA to promote ATP production. Accordingly, targeting SNHG17 with an antisense oligonucleotide significantly reduced breast cancer tumor growth both in vitro and in vivo. Overall, these results established a role for SNHG17 in promoting breast cancer progression by increasing ATP production and provided insights into the reprogramming of energy metabolism in solid tumors.Significance:SNHG17 cooperates with NF-κB to induce expression of mitochondrial DNA and boost ATP production in breast cancer, suggesting that targeting SNHG17 could reverse metabolic reprogramming to suppress tumor progression.

Tongue squamous cell carcinoma (TSCC) is an aggressive malignancy with poor prognosis and limited therapeutic options. Herbal medicines with multitarget activities and low toxicity have attracted increasing attention in cancer adjuvant therapy. This study aimed to investigate the anti-tumor effects and underlying mechanisms of the water extract of Andrographis paniculata (APW) in TSCC in vitro and in vivo. Two TSCC cell lines, Cal-27 and SCC25, were used for cell-based functional and mechanistic studies, while a Cal-27 xenograft-bearing mouse model was established for evaluating the in vivo effect of APW treatment. Our results showed that APW could significantly inhibit the proliferation of Cal-27 and SCC25 cells and induce apoptosis in a concentration-dependent manner. APW could promote mitochondrial-mediated apoptosis by upregulating Bax and cleaved caspase proteins but downregulating Bcl-2 in TSCC cells. It also suppressed the Wnt/β-catenin signaling pathway, reducing β-catenin expression and its downstream targets, CCND1, MYC, and JUN. Furthermore, APW disrupted mitochondrial integrity, induced cytochrome c release, and reduced mitochondrial membrane potential. APW also inhibited epithelial–mesenchymal transition, increasing E-cadherin and decreasing N-cadherin and vimentin expressions, thereby suppressing cell migration of TSCC cells. Furthermore, the 5-week APW treatment significantly reduced tumor growth and angiogenesis without evident hepatic or renal toxicity in Cal-27 xenograft-bearing mice. In conclusion, APW exerted potent anti-tumor effects by targeting both the Wnt/β-catenin pathway and mitochondrial apoptotic machinery, suggesting the great potential of APW as an adjuvant therapeutic candidate for TSCC treatment.