Overexpression of long noncoding RNA GAS5 suppresses tumorigenesis and development of gastric cancer by sponging miR-106a-5p through the Akt/mToR pathway

Abstract

Long non-coding RNAs (lncRNAs) have emerged as important regulators of human cancers. LncRNA GAS5 (GAS5) is identified tumor suppressor involved in several cancers. However, the roles of GAS5 and the mechanisms responsible for its functions in gastric cancer (GC) have not been well undocumented. Herein, the decreased GAS5 and increased miRNA-106a-5p levels were observed in GC and cell lines. GAS5 expression level was significantly inversely correlated with miRNA-106a-5p level in GC tissues. Moreover, luciferase reporter and qRT-PCR assays showed that GAS5 bound to miRNA-106a-5p and negatively regulated its expression in GC cells. Functional experiments showed that GAS5 overexpression suppressed GC cell proliferation, migration, and invasion capabilities and promoted apoptosis, while miRNA-106a-5p overexpression inversed the functional effects induced by GAS5 overexpression. In vivo, GAS5 overexpression inhibited tumor growth by negatively regulating miRNA-106a-5p expression. Mechanistic investigations revealed that GAS5 overexpression inactivating the Akt/mToR pathway by suppressing miRNA-106a-5p expression in vitro and in vivo. Taken together, our findings conclude the GAS5 overexpression suppresses tumorigenesis and development of gastric cancer by sponging miR-106a-5p through the Akt/mToR pathway. Keywords: GAS5; miR-106a-5p; gastric cancer; Akt/mToR pathway Conceptualization: S.D., X.Z.; Methodology: S.D., X.Z.; Software: D.L.; Validation: S.D., D.L.; Formal analysis: S.D., D.L.; Investigation: S.D., X.Z.

The Non-Coding RNA GAS5 and Its Role in Tumor Therapy-Induced Resistance

“…Gastric cancer is the fourth most common malignancy, and the second most common cause of cancer-related deaths in the world [ 60 ]. GAS5 also plays a significant role as a tumor suppressor in gastric cancer [ 61 , 62 , 63 , 64 ]. A recent study highlighted the fact that GAS5 expression was significantly down-regulated in gastric cancer tissues, and that it was down-regulated in adriamycin-resistant cells [ 65 ].…”

“…In gastric cancer, three miRNAs have been reported to relate to GAS5 , miR-18a [ 95 ], miR-106a-5p [ 63 ] and miR-222 [ 96 ]. In the case of miR-18a, it was reported that GAS5 directly binds to it, inhibiting tumor growth via the stimulation of the activity of natural killer (NK) cells [ 95 ].…”

“…In the case of miR-18a, it was reported that GAS5 directly binds to it, inhibiting tumor growth via the stimulation of the activity of natural killer (NK) cells [ 95 ]. On the other hand, GAS5 functions as sponge for miR-106a-5p, inactivating the Akt/mTOR pathway [ 63 ]. Finally, miR-222 was reported to directly bind to GAS5 similarly, as in all previous cases, suppressing tumor cell proliferation [ 96 ].…”

GAS5‑mediated regulation of cell signaling (Review)

“…one study reported that the expression level of GaS5 in gastric cancer is negatively associated with that of mir-106a-5p. overexpression of mir-106a-5p reverses the biological effects induced by GaS5 overexpression, which occurs via akt/mTor (49). This shows that GaS5 overexpression serves a role in inhibiting proliferation in gastric cancer cells by inhibiting the function of mir-106a-5p, thereby reducing mTor expression (49).…”

lncRNA TPTEP1 inhibits stemness and radioresistance of glioma through miR‑106a‑5p‑mediated P38 MAPK signaling

“…The results of the present study confirmed that mirna-106a-5p serves as an oncogene by augmenting TPTeP1-mediated stemness and radioresistance of glioma. Previous studies have demonstrated the stimulating effects of TPTeP1 and the inhibitory effect of mirna-106a-5p on cancer cell apoptosis (33,35,43). Thus, prospective studies will aim to elucidate the effect of TPTeP1 and mir-106-5p on glioma cell apoptosis.…”