TEPP-46-Based AIE Fluorescent Probe for Detection and Bioimaging of PKM2 in Living Cells

Abstract

Pyruvate kinase (PK) M2 (PKM2), a glycolytic enzyme, is a hallmark of different types of tumors and plays a significant role in the Warburg effect. However, there is no fluorescent probe for PKM2 that has been reported yet. In this study, TEPC466, a novel TEPP-46-based aggregation-induced emission (AIE) probe for the detection of PKM2, was designed, synthesized, and fully characterized by 1H NMR, 13C NMR, and high-resolution mass spectrometry. When the fluorescent agent, coumarine, was conjugated to TEPP-46, the bioprobe TEPC466 showed a high degree of selectivity and sensitivity for the detection of PKM2 protein via the AIE effect. TEPC466 was then successfully applied in imaging the PKM2 protein in colorectal cancer cells with low toxicity. Moreover, structure-based modeling and the PK activity assay confirmed that TEPC466 has a better binding with PKM2 than TEPP-46, which suggests that TEPC466 could also be a good agonist of PKM2. Taken together, the bioprobe shows potential in selective detection of PKM2 and provides a useful tool for cancer diagnosis and therapy.

Noncoding RNAs in the Glycolysis of Ovarian Cancer

“…The PKM gene encodes PKM1 and PKM2 through selective splicing ( Chen k et al, 2021 ; Itoyama et al, 2021 ). PKM1 is expressed in normal differentiated tissues ( Zhong et al, 2021 ), while PKM2 is expressed in highly proliferative cells such as embryonic cells, stem cells and tumor cells ( Wang et al, 2021 ). Physiologically, PKM1 exists as a tetramer, while PKM2 can exist as a tetramer or a dimer ( Hu et al, 2020 ; Rai et al, 2020 ).…”

“…Han et al, demonstrated that miR-383 regulates LDHA expression in OC cells, impeding glycolysis, cell proliferation and invasion ( Han et al, 2017 ). Tumor glycolytic activity is enhanced to adapt to ischemic and hypoxic environment by inducing an energy metabolic switch as the metabolic basis of its hypoxia tolerance ( Wang et al, 2021 ). This process activateshypoxia-inducible factor-1 (HIF-1), a widely present dominant oxygen regulator in mammals, triggers various biological events, including glycolytic activation and tumorigenesis ( Favier et al, 2015 ; Moldogazieva et al, 2020 ).…”

“…In summary, the circRNAs act as miRNA sponges and interact with RBPs to perform transcriptional functions in organisms. The open reading frames in circRNAs enrich exosomes and can be translated into polypeptides for early diagnosis and prognosis ( Kim H et al, 2021 ; Sinha et al, 2021 ; Wang et al, 2021 ). The circRNAs are critical in regulating the process of glycolysis in OC ( Table 3 ).…”

“…The development and progression of OC is a complex physiological process. The invasion and metastasis of OC is a complicated process, which poses difficulties for early detection, intervention, and treatment ( Tymon-Rosario et al, 2021 ; Wang et al, 2021 ). The Warburg effect is one of the recognized metabolic features of tumor cells ( Abi Zamer et al, 2021 ; Nakagawa et al, 2021 ).…”

“…NcRNAs are involved in a variety of life activities such as regulation of gene expression, intracellular signaling and epigenetic modifications. Apart from participation in tumorigenesis, ncRNAs also account paramount role in the glycolytic process of tumors ( Li Q et al, 2021 ; Lu et al, 2021 ; Park et al, 2021 ; Razavi et al, 2021 ; Wang et al, 2021 ). This review summarizes the possible molecular mechanisms of ncRNAs in the process of glycolysis and potentially effective targeted therapies for OC.…”