G allele of rs7853346 polymorphism in PTENP1 enhances the proliferation of multiple myeloma cancer stem cells by promoting the expression of PTENP1 and its downstream signaling molecules

Noncoding RNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), are shown to be associated with the pathogenesis of various diseases, such as multiple myeloma (MM). Therefore, the aim of this study was to explore the role of rs7853346 polymorphism in PTENP1, and its downstream signaling molecules, in the pathology of MM. Forty-three multiple myeloma patients and 35 healthy subjects were recruited and divided into CC, CG, and GG groups according to their genotypes of rs7853346 polymorphism in PTENP1. Real-time polymerase chain reaction (PCR), Western-blot analyses and immunohistochemistry assays were utilized to compare the expression of PTENP1, miR-19b, and TSC1 between different groups. In addition, the relationship between PTENP1, miR-19b, and TSC1, as well as the role of PTENP1 in MM, was explored. Higher levels of PTENP1 and TSC1 mesenger RNA (mRNA) were observed in the MM group, along with a lower level of miR-19b. Moreover, the protein level of TSC1 in the MM group was evidently upregulated compared to that in the negative control (NC) group. Meanwhile, compared to the CG and GG groups, the CC group showed higher levels of PTENP1 and TSC1 mRNA, as well as a lower level of miR-19b. According to the results of real-time PCR, a negative correlation with a correlation coefficient of -0.05 was established between PTENP1 and miR-19b expression. Similarly, a negative correlation with a correlation coefficient of -0.05 was also established between miR-19b and TSC1 expression. In addition, the transfection of pcDNA-PTENP1 or anti-miR-19b into cells significantly suppressed miR-19b expression but obviously increased TSC1 expression. The G allele of rs7853346 polymorphism enhances the proliferation of MM cancer stem cells by promoting the expression of PTENP1 as well as its downstream signaling molecules. Therefore, rs7853346 may become a novel biomarker for the diagnosis and treatment of MM.