LncRNA-GAS5 can act as a “sponge” for microRNA-21 (miR-21) by competitively sequestering miR-21 from binding target mRNAs. Moreover, miR-21 directly regulates PTEN and TPM1 via imperfect complementary target base pairing．We confirmed miR-21 regulates PTEN and TPM1 protein expression without significantly affecting PTEN and TPM1 mRNA expression via imperfect complementary target binding in HEK293T and HeLa cells. Furthermore, Overexpressing miR-21 could significantly shorten half-lives of PTEN and TPM1, miR-21 enhanced PTEN and TPM1 decay．Cells were transfected with lncRNA-GAS5 expression vector, we found lncRNA-GAS5 competitively bound miR-21 and increased the half-lives of PTEN and TPM1. Besides, miR-21 bound with lncRNA-GAS5 could lead rapid decay of lncRNA-GAS5. This study indicates lncRNA-GAS5 functions as a miR-21 “sponge” that inhibits mRNA degradation of the miR-21 imperfect complementary targets PTEN and TPM1, and miR-21 also could regulate lncRNA-GAS5 stability by base pairing．Further exploration of the mechanisms may improve our understanding of the lncRNA-miRNA-mRNA sophisticated regulatory feedback loop.