ZFPM2-AS1 transcriptionally mediated by STAT1 regulates thyroid cancer cell growth, migration and invasion via

Ruizhen Ren1, Yuanna Du2, Xing Niu3

  • 1Department of Endocrinology, Yantai Yuhuangding Hospital Affiliated to Qingdao University, Yantai 264000, Shandong, China.

Journal of Cancer
|May 12, 2021
PubMed

Insights

Long non-coding RNA ZFPM2-AS1 promotes thyroid cancer by acting as an oncogene. It is regulated by STAT1 and sponges miR-515-5p, inhibiting TUSC3 expression and enhancing cancer progression.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • Thyroid cancer is a significant health concern.
  • Long non-coding RNAs (lncRNAs) play crucial roles in various cancers.
  • The specific role of ZFPM2 Antisense RNA 1 (ZFPM2-AS1) in thyroid cancer requires further elucidation.

Purpose of the Study:

  • To investigate the roles and molecular mechanisms of lncRNA ZFPM2-AS1 in thyroid cancer.
  • To analyze the functional impact of ZFPM2-AS1 on thyroid cancer cell behavior.
  • To elucidate the regulatory pathways involving ZFPM2-AS1, miR-515-5p, and TUSC3.

Main Methods:

  • Expression analysis of ZFPM2-AS1, miR-515-5p, and TUSC3 in thyroid cancer tissues and cells.
  • Functional assays including CCK-8, clone formation, EdU, ELISA, wound healing, and Transwell assays to assess cell proliferation, apoptosis, migration, and invasion.
  • Mechanism validation using Chromatin Immunoprecipitation (CHIP), pull-down, and luciferase reporter assays.

Main Results:

  • ZFPM2-AS1 and TUSC3 were upregulated, while miR-515-5p was downregulated in thyroid cancer.
  • Knockdown of ZFPM2-AS1 inhibited thyroid cancer cell growth, migration, and invasion.
  • ZFPM2-AS1, regulated by STAT1, acts as a sponge for miR-515-5p, reducing its inhibition on TUSC3 and promoting cancer progression.

Conclusions:

  • ZFPM2-AS1 functions as an oncogene in thyroid cancer.
  • STAT1 transcriptionally upregulates ZFPM2-AS1.
  • ZFPM2-AS1 promotes thyroid cancer malignancy by sponging miR-515-5p and affecting TUSC3 expression, suggesting its potential as a biomarker.

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.0K
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
7.3K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.8K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
4.3K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
8.2K
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
4.8K