Tumor-suppressive miR-29c binds to MAPK1 inhibiting the ERK/MAPK pathway in pancreatic cancer

Hongtao Si1, Ning Zhang1, Chang Shi1

  • 1Department of Oncology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, People's Republic of China.

Abstract

Insights

MicroRNA-29c (miR-29c) suppresses pancreatic cancer by inhibiting the MAPK1 gene and the ERK/MAPK pathway. Restoring miR-29c levels reduced tumor growth in vitro and in vivo, indicating its potential as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Pancreatic cancer exhibits differential expression of microRNAs (miRNAs), including miR-29c.
  • Limited understanding of miR-29c's downstream mechanisms hinders therapeutic development for pancreatic cancer.

Purpose of the Study:

  • To elucidate the downstream targets and mechanistic actions of miR-29c in pancreatic cancer.
  • To investigate the role of the miR-29c/MAPK1/ERK/MAPK axis in pancreatic cancer progression.

Main Methods:

  • Bioinformatic prediction of miR-29c targets and the ERK/MAPK pathway.
  • Quantitative analysis of miR-29c and MAPK1 expression in pancreatic cancer tissues and cells.
  • In vitro functional assays (MTS, Transwell, flow cytometry) and in vivo xenograft models to assess miR-29c's impact on tumorigenesis.

Main Results:

  • miR-29c was identified as a key miRNA associated with pancreatic cancer prognosis and was downregulated in tumors.
  • miR-29c directly targets and inhibits MAPK1, suppressing the ERK/MAPK pathway.
  • Restoration of miR-29c inhibited cancer cell proliferation, migration, and invasion in vitro and suppressed tumor growth in vivo.

Conclusions:

  • A novel miR-29c/MAPK1/ERK/MAPK signaling axis was identified that suppresses pancreatic cancer.
  • miR-29c demonstrates significant anti-tumor activity, suggesting its potential as a therapeutic agent for pancreatic cancer.

Related Concept Videos

Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.4K
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...
3.9K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.8K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.6K
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...
4.6K
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...
3.8K