Long non‐coding RNA TNRC6C‐AS1 promotes methylation of STK4 to inhibit thyroid carcinoma cell apoptosis and autophagy via Hippo signalling pathway

Abstract

The role of long non‐coding RNAs (lncRNAs) in thyroid carcinoma (TC), the most frequent endocrine malignancy, has been extensively examined. This study investigated effect of interaction among lncRNA TNRC6C‐AS1, serine/threonine‐protein kinase 4 (STK4) and Hippo signalling pathway on TC. Initially, lncRNA TNRC6C‐AS1 expression in TC tissues was detected. To explore roles of lncRNA TNRC6C‐AS1, STK4 and Hippo signalling pathway in TC progression, their expressions were altered. Interaction between lncRNA TNRC6C‐AS1 and STK4, STK4 promoter methylation, or Hippo signalling pathway was verified. After that, a series of experiments were employed to evaluate in vitro ability of apoptosis, proliferation and autophagy of TC cells and in vivo tumorigenicity, and tumour growth of TC cells. lncRNA TNRC6C‐AS1 was highly expressed while STK4 was poorly expressed in TC tissues. LncRNA TNRC6C‐AS1 promoted the STK4 methylation and down‐regulated STK4 expression, which further activated the Hippo signalling pathway. STK4 silencing was observed to promote the proliferation ability of TC cells, inhibit the apoptosis and autophagy abilities, as well as enhance the tumorigenicity and tumour growth. Moreover, the in vitro proliferation ability as well as the in vivo tumorigenicity and tumour growth of TC cells were inhibited after the blockade of Hippo signalling pathway, while the apoptosis and autophagy abilities were promoted. The results demonstrate that the lncRNA TNRC6C‐AS1 increases STK4 promoter methylation to down‐regulate STK4 expression, thereby promoting the development of TC through activation of Hippo signalling pathway. It highlights that lncRNA TNRC6C‐AS1 may be a novel therapeutic target for the treatment of TC.

LncRNA LINC00857 regulates the progression and glycolysis in ovarian cancer by modulating the Hippo signaling pathway

“…In recent years, the Hippo signaling pathway has been found to be closely associated with tumor progression. For example, TNRC6C‐AS1 expedites the methylation of STK4 to inhibit thyroid carcinoma cell apoptosis through the Hippo signaling pathway 17 . HOX transcript antisense RNA directly binds to SAV1 and activates the Hippo pathway in renal cell carcinoma 18 …”

Identification of Cerebrospinal Fluid MicroRNAs Associated With Leptomeningeal Metastasis From Lung Adenocarcinoma

“…In addition, the four overlapping target genes of miR-7977 (CCL22, STK4, HSPA1B, and ACTR2) in all three databases were reported to have a key role in cancer formation and metastasis. Studies have shown that these genes are involved in the growth, invasion, and metastasis of a variety of tumors, and that they play a key role in tumorrelated molecular mechanisms (30)(31)(32)(33). Furthermore, abnormal signaling pathways also play crucial roles in the development of cancer metastasis.…”

Long non‐coding RNA UCA1 promotes autophagy by targeting miR‐96‐5p in acute myeloid leukaemia

“…Our preliminary studies also showed that knockdown of UCA1 had an inhibitory effect on AML cell proliferation in vitro and tumourigenesis in vivo. LncRNAs also function as crucial regulators of autophagy . Existing evidence suggests that UCA1 can regulate autophagy in several diseases, such as ischaemia‐reperfusion injury, colorectal cancer, and bladder cancer .…”

“…LncRNAs also function as crucial regulators of autophagy. 18,19 Existing evidence suggests that UCA1 can regulate autophagy in several diseases, such as ischaemia-reperfusion injury, 20 colorectal cancer, 21 and bladder cancer. 22 Nevertheless, the regulatory role and detailed mechanism of UCA1 in autophagy in AML remain unclear.…”