Long Noncoding RNA KLF3-AS1 Acts as an Endogenous RNA of miR-223 to Attenuate Gastric Cancer Progression and Chemoresistance

Abstract

Gastric cancer is a deadly disease, and the low rate of early diagnosis and chemoresistance largely contributed to the poor prognosis of gastric cancer. LncRNAs have been extensively reported for their roles in regulating cancer progression. In this study, we found that KLF3-AS1 was down-regulated in gastric cancer cells. Overexpression of KLF3-AS1 repressed gastric cancer cell proliferation, growth. In addition, KLF3-AS1 overexpression also exerted inhibitory effects on the gastric cancer cell invasion, migration and EMT, but promoted chemosensitivity of gastric cancer cells to cisplatin. The mechanistic studies showed that KLF3-AS1 could act as the “sponge” for miR-223 and to repress miR-223 expression in gastric cancer cells. Overexpression of miR-223 reversed the inhibitory effects of KLF3-AS1 overexpression on gastric cancer cell proliferation, invasion, migration and EMT, and attenuated the enhanced effects of KLF3-AS1 overexpression on gastric cancer cell chemosensitivity to cisplatin. The in vivo studies showed that KLF3-AS1 overexpression suppressed the tumor growth of SGC-7901 in the nude mice. In conclusion, our results for the first time demonstrated that KLF3-AS1 was down-regulated in gastric cancer cells and repressed gastric cancer cell proliferation, invasion, migration and EMT, and enhanced chemosensitivity to cisplatin. Further mechanistic results indicated that KLF3-AS1 exerted its biological function in gastric cancer cells by inhibiting miR-223 expression. Future studies are still required to decipher the detailed molecular mechanisms of KLF3-AS1 in gastric cancer.

Silencing of lncRNA KLF3‐AS1 represses cell growth in osteosarcoma via miR‐338‐3p/MEF2C axis

“…PCAT6 interference decreases cell viability and metastasis in OS 18 . However, in both ESCC and GC, the metastasis and proliferation of cancer cells may significantly be suppressed by KLF3‐AS1 overexpression 8,9 . Our results were opposite to these previous works as they indicated that knocking‐down KLF3‐AS1 did not only repress the in vitro cell proliferation, but it also limited in vivo tumor xenograft growth.…”

“…OS is one of the most prevalent bone malignancies among juveniles 16 . LncRNA KLF3‐AS1 is abnormally expressed and serves as an inhibitor in numerous human cancers, including ESCC 8 and GC 9 . In the current study, we demonstrated that, contrary to previous results, KLF3‐AS1 was overexpressed in OS cells and tumors.…”

“…On another case, the high expression of lncRNA SNHG4 can induce cell growth in OS 6 and is also closely associated with the poor prognosis of OS patients 7 . Notably, some recent researches demonstrated that lncRNA KLF3‐AS1, located at chromosome 4p14, has been confirmed to serve an anti‐tumor role in the development of esophageal squamous cell carcinoma 8 and gastric cancer 9 . Nonetheless, accurate knowledge on the function of KLF‐AS1 in the occurrence and development of OS is relatively rare.…”

“…7 Notably, some recent researches demonstrated that lncRNA KLF3-AS1, located at chromosome 4p14, has been confirmed to serve an anti-tumor role in the development of esophageal squamous cell carcinoma 8 and gastric cancer. 9 Nonetheless, accurate knowledge on the function of KLF-AS1 in the occurrence and development of OS is relatively rare. MicroRNAs (miRNAs), which are 16-25 nt in length, inversely regulate genes' expressions by degrading their target mRNAs.…”

A New Establishment of Cuproptosis-Related Long Non-Coding RNA Signature to Predict Prognosis in Head and Neck Squamous cell Carcinomas

“…Similarly, AC011462.4 was related with autophagy and veri ed with potential values on predicting renal cancer prognosis 36 . KLF3-AS1 can inhibit the expression of miR-223 to inhibit gastric cancer progression and resistance to chemotherapy 37 . What's more, KLF3-AS1 can attenuate miR-185-5p-mediated inhibition of KLF3 to impair cell migration and invasion 38 .…”