Intratumor Mycoplasma Promotes the Initiation and Progression of Hepatocellular Carcinoma

The carcinogenesis and progression of hepatocellular carcinoma (HCC) are closely related to viral infection and intestinal bacteria. However, little is known about the presence of bacteria within the HCC tumour microenvironment. Here, we show that the presence of the intratumor Mycoplasma hyorhinis(M. hyorhinis) promotes the initiation and progression of HCC by enhancing nuclear ploidy. We quantify M. hyorhinis in clinical tissue specimens of HCC and observe that patients with high M. hyorhinis load have a poor prognosis. And we found that gastrointestinal M. hyorhinis can retrogradely infect the liver through the oral-duodenal-hepatopancreatic ampulla route. We further show that the increases in nuclear ploidy and cancer stemness result from mitochondrial fission caused by intracellular M. hyorhinis. Mechanistically, M. hyorhinis infection promotes the decay of MFN1 mRNA in an m6A-dependent manner. Our findings indicate that M. hyorhinis infection promotes pathological polyploidization and suggest that Mycoplasma clearance with antibiotics or by regulating mitochondrial dynamics might have the potential for HCC therapy.