Provided are applications of an upstream Open Reading Frame (uORF) of a Phosphatase and Tensin homolog (PTEN) gene and a polypeptide coded by the same. A potential ORF of 96 bases (31aa-uORF) existing in the 5′ UTR of the PTEN can code an oligopeptide of 31 amino acids (named PTEN-31aa) and plays an important role in the development and progression process of tumors. Provided is a new diagnostic and therapeutic method and a drug screening platform for PTEN expression regulation related diseases, in particular gliomas. Also provided is a polypeptide for treatment of PTEN expression regulation related diseases.